pubblicazioni

@article{stephens_distinct_2013,

title = {Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.},

author = {Stephens, Sarah H. and Hartz, Sarah M. and Hoft, Nicole R. and Saccone, Nancy L. and Corley, Robin C. and Hewitt, John K. and Hopfer, Christian J. and Breslau, Naomi and Coon, Hilary and Chen, Xiangning and Ducci, Francesca and Dueker, Nicole and Franceschini, Nora and Frank, Josef and Han, Younghun and Hansel, Nadia N. and Jiang, Chenhui and Korhonen, Tellervo and Lind, Penelope A. and Liu, Jason and Lyytikainen, Leo-Pekka and Michel, Martha and Shaffer, John R. and Short, Susan E. and Sun, Juzhong and Teumer, Alexander and Thompson, John R. and Vogelzangs, Nicole and Vink, Jacqueline M. and Wenzlaff, Angela and Wheeler, William and Yang, Bao-Zhu and Aggen, Steven H. and Balmforth, Anthony J. and Baumeister, Sebastian E. and Beaty, Terri H. and Benjamin, Daniel J. and Bergen, Andrew W. and Broms, Ulla and Cesarini, David and Chatterjee, Nilanjan and Chen, Jingchun and Cheng, Yu-Ching and Cichon, Sven and Couper, David and Cucca, Francesco and Dick, Danielle and Foroud, Tatiana and Furberg, Helena and Giegling, Ina and Gillespie, Nathan A. and Gu, Fangyi and Hall, Alistair S. and Hallfors, Jenni and Han, Shizhong and Hartmann, Annette M. and Heikkila, Kauko and Hickie, Ian B. and Hottenga, Jouke Jan and Jousilahti, Pekka and Kaakinen, Marika and Kahonen, Mika and Koellinger, Philipp D. and Kittner, Stephen and Konte, Bettina and Landi, Maria-Teresa and Laatikainen, Tiina and Leppert, Mark and Levy, Steven M. and Mathias, Rasika A. and McNeil, Daniel W. and Medland, Sarah E. and Montgomery, Grant W. and Murray, Tanda and Nauck, Matthias and North, Kari E. and Pare, Peter D. and Pergadia, Michele and Ruczinski, Ingo and Salomaa, Veikko and Viikari, Jorma and Willemsen, Gonneke and Barnes, Kathleen C. and Boerwinkle, Eric and Boomsma, Dorret I. and Caporaso, Neil and Edenberg, Howard J. and Francks, Clyde and Gelernter, Joel and Grabe, Hans Jorgen and Hops, Hyman and Jarvelin, Marjo-Riitta and Johannesson, Magnus and Kendler, Kenneth S. and Lehtimaki, Terho and Magnusson, Patrik K. E. and Marazita, Mary L. and Marchini, Jonathan and Mitchell, Braxton D. and Nothen, Markus M. and Penninx, Brenda W. and Raitakari, Olli and Rietschel, Marcella and Rujescu, Dan and Samani, Nilesh J. and Schwartz, Ann G. and Shete, Sanjay and Spitz, Margaret and Swan, Gary E. and Volzke, Henry and Veijola, Juha and Wei, Qingyi and Amos, Chris and Cannon, Dale S. and Grucza, Richard and Hatsukami, Dorothy and Heath, Andrew and Johnson, Eric O. and Kaprio, Jaakko and Madden, Pamela and Martin, Nicholas G. and Stevens, Victoria L. and Weiss, Robert B. and Kraft, Peter and Bierut, Laura J. and Ehringer, Marissa A.},

doi = {10.1002/gepi.21760},

issn = {1098-2272 0741-0395},

year  = {2013},

date = {2013-12-01},

journal = {Genet Epidemiol},

volume = {37},

number = {8},

pages = {846--859},

abstract = {Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{yamamoto_nebulin_2013,

title = {The nebulin SH3 domain is dispensable for normal skeletal muscle structure but is required for effective active load bearing in mouse},

author = {Daniel L Yamamoto and Carmen Vitiello and Jianlin Zhang and David S Gokhin and Alessandra Castaldi and Gerald Coulis and Fabio Piaser and Maria Carmela Filomena and Peter J Eggenhuizen and Paolo Kunderfranco and Serena Camerini and Kazunori Takano and Takeshi Endo and Marco Crescenzi and Pradeep K L Luther and Richard L Lieber and Ju Chen and Marie-Louise Bang},

doi = {10.1242/jcs.137026},

issn = {1477-9137},

year  = {2013},

date = {2013-12-01},

journal = {Journal of Cell Science},

volume = {126},

number = {Pt 23},

pages = {5477--5489},

abstract = {Nemaline myopathy (NM) is a congenital myopathy with an estimated incidence of 150,000 live births. It is caused by mutations in thin filament components, including nebulin, which accounts for about 50% of the cases. The identification of NM cases with nonsense mutations resulting in loss of the extreme C-terminal SH3 domain of nebulin suggests an important role of the nebulin SH3 domain, which is further supported by the recent demonstration of its role in IGF-1-induced sarcomeric actin filament formation through targeting of N-WASP to the Z-line. To provide further insights into the functional significance of the nebulin SH3 domain in the Z-disk and to understand the mechanisms by which truncations of nebulin lead to NM, we took two approaches: (1) an affinity-based proteomic screening to identify novel interaction partners of the nebulin SH3 domain; and (2) generation and characterization of a novel knockin mouse model with a premature stop codon in the nebulin gene, eliminating its C-terminal SH3 domain (NebδSH3 mouse). Surprisingly, detailed analyses of NebδSH3 mice revealed no structural or histological skeletal muscle abnormalities and no changes in gene expression or localization of interaction partners of the nebulin SH3 domain, including myopalladin, palladin, zyxin and N-WASP. Also, no significant effect on peak isometric stress production, passive tensile stress or Young's modulus was found. However, NebδSH3 muscle displayed a slightly altered force-frequency relationship and was significantly more susceptible to eccentric contraction-induced injury, suggesting that the nebulin SH3 domain protects against eccentric contraction-induced injury and possibly plays a role in fine-tuning the excitation-contraction coupling mechanism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{terracciano_genetics_2013,

title = {Genetics of serum BDNF: meta-analysis of the Val66Met and genome-wide association study},

author = {Antonio Terracciano and Maria Grazia Piras and Monia Lobina and Antonella Mulas and Osorio Meirelles and Angelina R Sutin and Wayne Chan and Serena Sanna and Manuela Uda and Laura Crisponi and David Schlessinger},

doi = {10.3109/15622975.2011.616533},

issn = {1814-1412},

year  = {2013},

date = {2013-12-01},

journal = {The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of Biological Psychiatry},

volume = {14},

number = {8},

pages = {583--589},

abstract = {OBJECTIVES: Lower levels of serum brain derived neurotrophic factor (BDNF) is one of the best known biomarkers of depression. To identify genetic variants associated with serum BDNF, we tested the Val66Met (rs6265) functional variant and conducted a genome-wide association scan (GWAS). METHODS: In a community-based sample (N = 2054; aged 19-101},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{forabosco_insights_2013,

title = {Insights into TREM2 biology by network analysis of human brain gene expression data},

author = {Paola Forabosco and Adaikalavan Ramasamy and Daniah Trabzuni and Robert Walker and Colin Smith and Jose Bras and Adam P Levine and John Hardy and Jennifer M Pocock and Rita Guerreiro and Michael E Weale and Mina Ryten},

doi = {10.1016/j.neurobiolaging.2013.05.001},

issn = {1558-1497},

year  = {2013},

date = {2013-12-01},

journal = {Neurobiology of Aging},

volume = {34},

number = {12},

pages = {2699--2714},

abstract = {Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease. Here we use microarray-based expression data generated from 101 neuropathologically normal individuals and covering 10 brain regions, including the hippocampus, to understand TREM2 biology in human brain. Using network analysis, we detect a highly preserved TREM2-containing module in human brain, show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5 brain regions, including the hippocampus, suggesting that it can drive module function. Using enrichment analysis we show significant overrepresentation of genes implicated in the adaptive and innate immune system. Inspection of genes with the highest connectivity to TREM2 suggests that it plays a key role in mediating changes in the microglial cytoskeleton necessary not only for phagocytosis, but also migration. Most importantly, we show that the TREM2-containing module is significantly enriched for genes genetically implicated in Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia and that among the genes identified are possible new disease-relevant genes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23486543,

title = {The homozygosity index (HI) approach reveals high allele frequency for Wilson disease in the Sardinian population},

author = {A. Gialluisi and S. Incollu and T. Pippucci and M. B. Lepori and A. Zappu and G. Loudianos and G. Romeo},

year  = {2013},

date = {2013-11-01},

urldate = {2013-11-01},

journal = {Eur J Hum Genet},

volume = {21},

number = {11},

pages = {1308--1311},

abstract = {10(-4)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{khurana_integrative_2013,

title = {Integrative annotation of variants from 1092 humans: application to cancer genomics.},

author = {Khurana, Ekta and Fu, Yao and Colonna, Vincenza and Mu, Xinmeng Jasmine and Kang, Hyun Min and Lappalainen, Tuuli and Sboner, Andrea and Lochovsky, Lucas and Chen, Jieming and Harmanci, Arif and Das, Jishnu and Abyzov, Alexej and Balasubramanian, Suganthi and Beal, Kathryn and Chakravarty, Dimple and Challis, Daniel and Chen, Yuan and Clarke, Declan and Clarke, Laura and Cunningham, Fiona and Evani, Uday S. and Flicek, Paul and Fragoza, Robert and Garrison, Erik and Gibbs, Richard and Gumus, Zeynep H. and Herrero, Javier and Kitabayashi, Naoki and Kong, Yong and Lage, Kasper and Liluashvili, Vaja and Lipkin, Steven M. and MacArthur, Daniel G. and Marth, Gabor and Muzny, Donna and Pers, Tune H. and Ritchie, Graham R. S. and Rosenfeld, Jeffrey A. and Sisu, Cristina and Wei, Xiaomu and Wilson, Michael and Xue, Yali and Yu, Fuli and Dermitzakis, Emmanouil T. and Yu, Haiyuan and Rubin, Mark A. and Tyler-Smith, Chris and Gerstein, Mark},

doi = {10.1126/science.1235587},

issn = {1095-9203 0036-8075},

year  = {2013},

date = {2013-10-01},

journal = {Science},

volume = {342},

number = {6154},

pages = {1235587},

abstract = {Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, "motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e.g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool (FunSeq), whose application to textasciitilde90 cancer genomes reveals nearly a hundred candidate noncoding drivers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{muntoni_high_2013,

title = {High meat consumption is associated with type 1 diabetes mellitus in a Sardinian case-control study.},

author = {Muntoni, Sandro and Mereu, Roberto and Atzori, Luigi and Mereu, Alessandra and Galassi, Sabrina and Corda, Stefania and Frongia, Paola and Angius, Efisio and Pusceddu, Paolo and Contu, Paolo and Cucca, Francesco and Congia, Mauro and Muntoni, Sergio},

doi = {10.1007/s00592-012-0385-2},

issn = {1432-5233 0940-5429},

year  = {2013},

date = {2013-10-01},

journal = {Acta Diabetol},

volume = {50},

number = {5},

pages = {713--719},

abstract = {The large worldwide variation in type 1 diabetes incidence and increasing incidence over time points toward important environmental risk factors. Among them, nutrition plays an important role. The objective was to investigate the relationship between type 1 diabetes and nutritional factors in pregnancy and early in life. We carried out, using semi-quantitative food frequency questionnaires, a retrospective case-control study in 298 children of 0-15 years old, 145 of which were affected by type 1 diabetes. The diet of all children and of their mothers during pregnancy and lactation was assessed. In children, a statistically significant dose-response association between type 1 diabetes and the amount of meat consumption was found while no other nutritional factors were associated with the disease. High meat consumption seems to be an important early in life cofactor for type 1 diabetes development, although these findings need to be confirmed in wider prospective follow-up studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{di_pasquale_camkii_2013,

title = {CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of catecholaminergic polymorphic ventricular tachycardia},

author = {E {Di Pasquale} and F Lodola and M Miragoli and M Denegri and J E Avelino-Cruz and M Buonocore and H Nakahama and P Portararo and R Bloise and C Napolitano and G Condorelli and S G Priori},

doi = {10.1038/cddis.2013.369},

issn = {2041-4889},

year  = {2013},

date = {2013-10-01},

journal = {Cell Death & Disease},

volume = {4},

pages = {e843},

abstract = {Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro 'patient-specific cell-based system' that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac model of CPVT through the generation of iPSC from a CPVT patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene (RyR2) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after β-adrenergic stimulation, resembling the cardiac phenotype of the patients. Furthermore, treatment with KN-93 (2-[N-(2-hydroxyethyl)]-N-(4methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), an antiarrhythmic drug that inhibits Ca(2+)/calmodulin-dependent serine-threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2013-pb,

title = {Genetic variants regulating immune cell levels in health and  disease},

author = {Valeria Örr`u and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonc calo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco" Cucca},

doi = {10.1016/j.cell.2013.08.041},

year  = {2013},

date = {2013-09-01},

urldate = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the 

 immune system has evolved to defend against pathogens, but 

 inadvertent immune system attacks on ``self'' result in 

 autoimmune disease. Both genetic regulation of immune cell levels 

 and their relationships with autoimmunity are largely 

 undetermined. Here, we report genetic contributions to 

 quantitative levels of 95 cell types encompassing 272 immune 

 traits, in a cohort of 1,629 individuals from four clustered 

 Sardinian villages. We first estimated trait heritability, 

 showing that it can be substantial, accounting for up to 87% of 

 the variance (mean 41%). Next, by assessing ∼8.2 million 

 variants that we identified and confirmed in an extended set of 

 2,870 individuals, 23 independent variants at 13 loci associated 

 with at least one trait. Notably, variants at three loci (HLA, 

 IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease 

 associations. These results connect specific cellular phenotypes 

 to specific genetic variants, helping to explicate their 

 involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2013-rl,

title = {Genetic variants regulating immune cell levels in health and  disease},

author = {Valeria Örr`u and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonc calo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco" Cucca},

doi = {10.1016/j.cell.2013.08.041},

year  = {2013},

date = {2013-09-01},

urldate = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the 

 immune system has evolved to defend against pathogens, but 

 inadvertent immune system attacks on ``self'' result in 

 autoimmune disease. Both genetic regulation of immune cell levels 

 and their relationships with autoimmunity are largely 

 undetermined. Here, we report genetic contributions to 

 quantitative levels of 95 cell types encompassing 272 immune 

 traits, in a cohort of 1,629 individuals from four clustered 

 Sardinian villages. We first estimated trait heritability, 

 showing that it can be substantial, accounting for up to 87% of 

 the variance (mean 41%). Next, by assessing ∼8.2 million 

 variants that we identified and confirmed in an extended set of 

 2,870 individuals, 23 independent variants at 13 loci associated 

 with at least one trait. Notably, variants at three loci (HLA, 

 IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease 

 associations. These results connect specific cellular phenotypes 

 to specific genetic variants, helping to explicate their 

 involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2013-epd,

title = {Genetic variants regulating immune cell levels in health and 

 disease},

author = {Valeria Örr`u and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonc calo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco" Cucca},

year  = {2013},

date = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the 

 immune system has evolved to defend against pathogens, but 

 inadvertent immune system attacks on ``self'' result in 

 autoimmune disease. Both genetic regulation of immune cell levels 

 and their relationships with autoimmunity are largely 

 undetermined. Here, we report genetic contributions to 

 quantitative levels of 95 cell types encompassing 272 immune 

 traits, in a cohort of 1,629 individuals from four clustered 

 Sardinian villages. We first estimated trait heritability, 

 showing that it can be substantial, accounting for up to 87% of 

 the variance (mean 41%). Next, by assessing ∼8.2 million 

 variants that we identified and confirmed in an extended set of 

 2,870 individuals, 23 independent variants at 13 loci associated 

 with at least one trait. Notably, variants at three loci (HLA, 

 IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease 

 associations. These results connect specific cellular phenotypes 

 to specific genetic variants, helping to explicate their 

 involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2013-epc,

title = {Genetic variants regulating immune cell levels in health and 

 disease},

author = {Valeria Örr`u and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonc calo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco" Cucca},

year  = {2013},

date = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the 

 immune system has evolved to defend against pathogens, but 

 inadvertent immune system attacks on ``self'' result in 

 autoimmune disease. Both genetic regulation of immune cell levels 

 and their relationships with autoimmunity are largely 

 undetermined. Here, we report genetic contributions to 

 quantitative levels of 95 cell types encompassing 272 immune 

 traits, in a cohort of 1,629 individuals from four clustered 

 Sardinian villages. We first estimated trait heritability, 

 showing that it can be substantial, accounting for up to 87% of 

 the variance (mean 41%). Next, by assessing ∼8.2 million 

 variants that we identified and confirmed in an extended set of 

 2,870 individuals, 23 independent variants at 13 loci associated 

 with at least one trait. Notably, variants at three loci (HLA, 

 IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease 

 associations. These results connect specific cellular phenotypes 

 to specific genetic variants, helping to explicate their 

 involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2013-epb,

title = {Genetic variants regulating immune cell levels in health and  disease},

author = {Valeria Örr`u and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonc calo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco" Cucca},

doi = {10.1016/j.cell.2013.08.041},

year  = {2013},

date = {2013-09-01},

urldate = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the 

 immune system has evolved to defend against pathogens, but 

 inadvertent immune system attacks on ``self'' result in 

 autoimmune disease. Both genetic regulation of immune cell levels 

 and their relationships with autoimmunity are largely 

 undetermined. Here, we report genetic contributions to 

 quantitative levels of 95 cell types encompassing 272 immune 

 traits, in a cohort of 1,629 individuals from four clustered 

 Sardinian villages. We first estimated trait heritability, 

 showing that it can be substantial, accounting for up to 87% of 

 the variance (mean 41%). Next, by assessing ∼8.2 million 

 variants that we identified and confirmed in an extended set of 

 2,870 individuals, 23 independent variants at 13 loci associated 

 with at least one trait. Notably, variants at three loci (HLA, 

 IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease 

 associations. These results connect specific cellular phenotypes 

 to specific genetic variants, helping to explicate their 

 involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2013-ep,

title = {Genetic variants regulating immune cell levels in health and 

 disease},

author = {Valeria Örr`u and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonc calo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco" Cucca},

year  = {2013},

date = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the 

 immune system has evolved to defend against pathogens, but 

 inadvertent immune system attacks on ``self'' result in 

 autoimmune disease. Both genetic regulation of immune cell levels 

 and their relationships with autoimmunity are largely 

 undetermined. Here, we report genetic contributions to 

 quantitative levels of 95 cell types encompassing 272 immune 

 traits, in a cohort of 1,629 individuals from four clustered 

 Sardinian villages. We first estimated trait heritability, 

 showing that it can be substantial, accounting for up to 87% of 

 the variance (mean 41%). Next, by assessing ∼8.2 million 

 variants that we identified and confirmed in an extended set of 

 2,870 individuals, 23 independent variants at 13 loci associated 

 with at least one trait. Notably, variants at three loci (HLA, 

 IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease 

 associations. These results connect specific cellular phenotypes 

 to specific genetic variants, helping to explicate their 

 involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2013-qe,

title = {Genetic variants regulating immune cell levels in health and 

 disease},

author = {Valeria Örr`u and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonc calo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco" Cucca},

year  = {2013},

date = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the 

 immune system has evolved to defend against pathogens, but 

 inadvertent immune system attacks on ``self'' result in 

 autoimmune disease. Both genetic regulation of immune cell levels 

 and their relationships with autoimmunity are largely 

 undetermined. Here, we report genetic contributions to 

 quantitative levels of 95 cell types encompassing 272 immune 

 traits, in a cohort of 1,629 individuals from four clustered 

 Sardinian villages. We first estimated trait heritability, 

 showing that it can be substantial, accounting for up to 87% of 

 the variance (mean 41%). Next, by assessing ∼8.2 million 

 variants that we identified and confirmed in an extended set of 

 2,870 individuals, 23 independent variants at 13 loci associated 

 with at least one trait. Notably, variants at three loci (HLA, 

 IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease 

 associations. These results connect specific cellular phenotypes 

 to specific genetic variants, helping to explicate their 

 involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2013-us,

title = {Genetic variants regulating immune cell levels in health and 

 disease},

author = {Valeria Örr`u and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonc calo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco" Cucca},

year  = {2013},

date = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the 

 immune system has evolved to defend against pathogens, but 

 inadvertent immune system attacks on ``self'' result in 

 autoimmune disease. Both genetic regulation of immune cell levels 

 and their relationships with autoimmunity are largely 

 undetermined. Here, we report genetic contributions to 

 quantitative levels of 95 cell types encompassing 272 immune 

 traits, in a cohort of 1,629 individuals from four clustered 

 Sardinian villages. We first estimated trait heritability, 

 showing that it can be substantial, accounting for up to 87% of 

 the variance (mean 41%). Next, by assessing ∼8.2 million 

 variants that we identified and confirmed in an extended set of 

 2,870 individuals, 23 independent variants at 13 loci associated 

 with at least one trait. Notably, variants at three loci (HLA, 

 IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease 

 associations. These results connect specific cellular phenotypes 

 to specific genetic variants, helping to explicate their 

 involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23969696,

title = {Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease},

author = { M. Sabater-Lleal and J. Huang and D. Chasman and S. Naitza and A. Dehghan and A. D. Johnson and others},

year  = {2013},

date = {2013-09-01},

journal = {Circulation},

volume = {128},

number = {12},

pages = {1310--1324},

abstract = {Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24074872,

title = {Genetic variants regulating immune cell levels in health and disease},

author = { },

year  = {2013},

date = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one trait. Notably, variants at three loci (HLA, IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease associations. These results connect specific cellular phenotypes to specific genetic variants, helping to explicate their involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{graff_genome-wide_2013,

title = {Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course.},

author = {Graff, Mariaelisa and Ngwa, Julius S. and Workalemahu, Tsegaselassie and Homuth, Georg and Schipf, Sabine and Teumer, Alexander and Volzke, Henry and Wallaschofski, Henri and Abecasis, Goncalo R. and Edward, Lakatta and Francesco, Cucca and Sanna, Serena and Scheet, Paul and Schlessinger, David and Sidore, Carlo and Xiao, Xiangjun and Wang, Zhaoming and Chanock, Stephen J. and Jacobs, Kevin B. and Hayes, Richard B. and Hu, Frank and Van Dam, Rob M. and Crout, Richard J. and Marazita, Mary L. and Shaffer, John R. and Atwood, Larry D. and Fox, Caroline S. and Heard-Costa, Nancy L. and White, Charles and Choh, Audrey C. and Czerwinski, Stefan A. and Demerath, Ellen W. and Dyer, Thomas D. and Towne, Bradford and Amin, Najaf and Oostra, Ben A. and Van Duijn, Cornelia M. and Zillikens, M. Carola and Esko, Tonu and Nelis, Mari and Nikopensius, Tit and Metspalu, Andres and Strachan, David P. and Monda, Keri and Qi, Lu and North, Kari E. and Cupples, L. Adrienne and Gordon-Larsen, Penny and Berndt, Sonja I.},

doi = {10.1093/hmg/ddt205},

issn = {1460-2083 0964-6906},

year  = {2013},

date = {2013-09-01},

journal = {Hum Mol Genet},

volume = {22},

number = {17},

pages = {3597--3607},

abstract = {Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P textless 5.0 x 10(-)(8)) near FTO (P = 3.72 x 10(-)(2)(3)), TMEM18 (P = 3.24 x 10(-)(1)(7)), MC4R (P = 4.41 x 10(-)(1)(7)), TNNI3K (P = 4.32 x 10(-)(1)(1)), SEC16B (P = 6.24 x 10(-)(9)), GNPDA2 (P = 1.11 x 10(-)(8)) and POMC (P = 4.94 x 10(-)(8)) as well as a potential secondary signal at the POMC locus (rs2118404},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sobacchi_osteopetrosis:_2013,

title = {Osteopetrosis: genetics, treatment and new insights into osteoclast function},

author = {Cristina Sobacchi and Ansgar Schulz and Fraser P Coxon and Anna Villa and Miep H Helfrich},

doi = {10.1038/nrendo.2013.137},

issn = {1759-5037},

year  = {2013},

date = {2013-09-01},

journal = {Nature Reviews. Endocrinology},

volume = {9},

number = {9},

pages = {522--536},

abstract = {Osteopetrosis is a genetic condition of increased bone mass, which is caused by defects in osteoclast formation and function. Both autosomal recessive and autosomal dominant forms exist, but this Review focuses on autosomal recessive osteopetrosis (ARO), also known as malignant infantile osteopetrosis. The genetic basis of this disease is now largely uncovered: mutations in TCIRG1, CLCN7, OSTM1, SNX10 and PLEKHM1 lead to osteoclast-rich ARO (in which osteoclasts are abundant but have severely impaired resorptive function), whereas mutations in TNFSF11 and TNFRSF11A lead to osteoclast-poor ARO. In osteoclast-rich ARO, impaired endosomal and lysosomal vesicle trafficking results in defective osteoclast ruffled-border formation and, hence, the inability to resorb bone and mineralized cartilage. ARO presents soon after birth and can be fatal if left untreated. However, the disease is heterogeneous in clinical presentation and often misdiagnosed. This article describes the genetics of ARO and discusses the diagnostic role of next-generation sequencing methods. The management of affected patients, including guidelines for the indication of haematopoietic stem cell transplantation (which can provide a cure for many types of ARO), are outlined. Finally, novel treatments, including preclinical data on in utero stem cell treatment, RANKL replacement therapy and denosumab therapy for hypercalcaemia are also discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{orru_genetic_2013,

title = {Genetic variants regulating immune cell levels in health and disease.},

author = {Valeria Orrù and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gon{ç}alo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco Cucca},

doi = {10.1016/j.cell.2013.08.041},

issn = {1097-4172},

year  = {2013},

date = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--56},

abstract = {The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one trait. Notably, variants at three loci (HLA, IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease associations. These results connect specific cellular phenotypes to specific genetic variants, helping to explicate their involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{francalacci_low-pass_2013,

title = {Low-pass DNA sequencing of 1200 Sardinians reconstructs European Y-chromosome phylogeny},

author = {Paolo Francalacci and Laura Morelli and Andrea Angius and Riccardo Berutti and Frederic Reinier and Rossano Atzeni and Rosella Pilu and Fabio Busonero and Andrea Maschio and Ilenia Zara and Daria Sanna and Antonella Useli and Maria Francesca Urru and Marco Marcelli and Roberto Cusano and Manuela Oppo and Magdalena Zoledziewska and Maristella Pitzalis and Francesca Deidda and Eleonora Porcu and Fausto Poddie and Hyun Min Kang and Robert Lyons and Brendan Tarrier and Jennifer Bragg Gresham and Bingshan Li and Sergio Tofanelli and Santos Alonso and Mariano Dei and Sandra Lai and Antonella Mulas and Michael B Whalen and Sergio Uzzau and Chris Jones and David Schlessinger and Gon{ç}alo R Abecasis and Serena Sanna and Carlo Sidore and Francesco Cucca},

doi = {10.1126/science.1237947},

issn = {1095-9203},

year  = {2013},

date = {2013-08-01},

journal = {Science (New York, N.Y.)},

volume = {341},

number = {6145},

pages = {565--569},

abstract = {Genetic variation within the male-specific portion of the Y chromosome (MSY) can clarify the origins of contemporary populations, but previous studies were hampered by partial genetic information. Population sequencing of 1204 Sardinian males identified 11,763 MSY single-nucleotide polymorphisms, 6751 of which have not previously been observed. We constructed a MSY phylogenetic tree containing all main haplogroups found in Europe, along with many Sardinian-specific lineage clusters within each haplogroup. The tree was calibrated with archaeological data from the initial expansion of the Sardinian population textasciitilde7700 years ago. The ages of nodes highlight different genetic strata in Sardinia and reveal the presumptive timing of coalescence with other human populations. We calculate a putative age for coalescence of textasciitilde180,000 to 200,000 years ago, which is consistent with previous mitochondrial DNA-based estimates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{paul_maps_2013,

title = {Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci.},

author = {Paul, Dirk S. and Albers, Cornelis A. and Rendon, Augusto and Voss, Katrin and Stephens, Jonathan and van der Harst, Pim and Chambers, John C. and Soranzo, Nicole and Ouwehand, Willem H. and Deloukas, Panos},

doi = {10.1101/gr.155127.113},

issn = {1549-5469 1088-9051},

year  = {2013},

date = {2013-07-01},

journal = {Genome Res},

volume = {23},

number = {7},

pages = {1130--1141},

abstract = {Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type-specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ficara_pbx1_2013,

title = {Pbx1 restrains myeloid maturation while preserving lymphoid potential in hematopoietic progenitors},

author = {Francesca Ficara and Laura Crisafulli and Chenwei Lin and Masayuki Iwasaki and Kevin S Smith and Luca Zammataro and Michael L Cleary},

doi = {10.1242/jcs.125435},

issn = {1477-9137},

year  = {2013},

date = {2013-07-01},

journal = {Journal of Cell Science},

volume = {126},

number = {Pt 14},

pages = {3181--3191},

abstract = {The capacity of the hematopoietic system to promptly respond to peripheral demands relies on adequate pools of progenitors able to transiently proliferate and differentiate in a regulated manner. However, little is known about factors that may restrain progenitor maturation to maintain their reservoirs. Conditional knockout mice for the Pbx1 proto-oncogene have a significant reduction in lineage-restricted progenitors in addition to a profound defect in hematopoietic stem cell (HSC) self-renewal. Through analysis of purified progenitor proliferation, differentiation capacity and transcriptional profiling, we demonstrate that Pbx1 regulates the lineage-specific output of multipotent and oligopotent progenitors. In the absence of Pbx1 multipotent progenitor (MPP) and common myeloid progenitor (CMP) pools are reduced due to aberrantly rapid myeloid maturation. This is associated with premature expression of myeloid differentiation genes and decreased maintenance of proto-oncogene transcriptional pathways, including reduced expression of Meis1, a Pbx1 dimerization partner, and its subordinate transcriptional program. Conversely, Pbx1 maintains the lymphoid differentiation potential of lymphoid-primed MPPs (LMPPs) and common lymphoid progenitors (CLPs), whose reduction in the absence of Pbx1 is associated with a defect in lymphoid priming that is also present in CMPs, which persistently express lymphoid and HSC genes underlying a previously unappreciated lineage promiscuity that is maintained by Pbx1. These results demonstrate a role for Pbx1 in restraining myeloid maturation while maintaining lymphoid potential to appropriately regulate progenitor reservoirs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23436819,

title = {An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart},

author = {E Tritsch and Y Mallat and F Lefebvre and N Diguet and B Escoubet and J Blanc and L J De Windt and D Catalucci and G Vandecasteele and Z Li and M Mericskay},

year  = {2013},

date = {2013-06-01},

journal = {Cardiovasc Res},

volume = {98},

number = {3},

pages = {372--380},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23624599,

title = {Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells},

author = {Gagliani, N. and Magnani, C. F. and Huber, S. and Gianolini, M. E. and Pala, M. and Licona-Limon, P. and Guo, B. and Herbert, D. R. and Bulfone, A. and Trentini, F. and Di Serio, C. and Bacchetta, R. and Andreani, M. and Brockmann, L. and Gregori, S. and Flavell, R. A. and Roncarolo, M. G.},

year  = {2013},

date = {2013-06-01},

journal = {Nat Med},

volume = {19},

number = {6},

pages = {739--746},

abstract = {CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sutin_personality_2013,

title = {Personality traits and leptin.},

author = {Sutin, Angelina R. and Zonderman, Alan B. and Uda, Manuela and Deiana, Barbara and Taub, Dennis D. and Longo, Dan L. and Ferrucci, Luigi and Schlessinger, David and Cucca, Francesco and Terracciano, Antonio},

doi = {10.1097/PSY.0b013e3182919ff4},

issn = {1534-7796 0033-3174},

year  = {2013},

date = {2013-06-01},

journal = {Psychosom Med},

volume = {75},

number = {5},

pages = {505--509},

abstract = {OBJECTIVE: Personality traits related to high neuroticism and low conscientiousness are consistently associated with obesity. Hormones implicated in appetite and metabolism, such as leptin, may also be related to personality and may contribute to the association between these traits and obesity. The present research examined the association between leptin and Five Factor Model personality traits. METHODS: A total of 5214 participants (58% women; mean [standard deviation] age = 44.42 [15.93] years; range, 18-94 years) from the SardiNIA project completed the Revised NEO Personality Inventory, a comprehensive measure of personality traits, and their blood samples were assayed for leptin. RESULTS: As expected, lower conscientiousness was associated with higher circulating levels of leptin (r = -0.05, p textless .001), even after controlling for body mass index, waist circumference, or inflammatory markers (r = -0.05, p textless .001). Neuroticism, in contrast, was unrelated to leptin (r = 0.01},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{meirelles_shave:_2013,

title = {SHAVE: shrinkage estimator measured for multiple visits increases power in GWAS of quantitative traits.},

author = {Meirelles, Osorio D. and Ding, Jun and Tanaka, Toshiko and Sanna, Serena and Yang, Hsih-Te and Dudekula, Dawood B. and Cucca, Francesco and Ferrucci, Luigi and Abecasis, Goncalo and Schlessinger, David},

doi = {10.1038/ejhg.2012.215},

issn = {1476-5438 1018-4813},

year  = {2013},

date = {2013-06-01},

journal = {Eur J Hum Genet},

volume = {21},

number = {6},

pages = {673--679},

abstract = {Measurement error and biological variability generate distortions in quantitative phenotypic data. In longitudinal studies with repeated measurements, the multiple measurements provide a route to reduce noise and correspondingly increase the strength of signals in genome-wide association studies (GWAS).To optimize noise correction, we have developed Shrunken Average (SHAVE), an approach using a Bayesian Shrinkage estimator. This estimator uses regression toward the mean for every individual as a function of (1) their average across visits; (2) their number of visits; and (3) the correlation between visits. Computer simulations support an increase in power, with results very similar to those expected by the assumptions of the model. The method was applied to a real data set for 14 anthropomorphic traits in approximately 6000 individuals enrolled in the SardiNIA project, with up to three visits (measurements) for each participant. Results show that additional measurements have a large impact on the strength of GWAS signals, especially when participants have different number of visits, with SHAVE showing a clear increase in power relative to single visits. In addition, we have derived a relation to assess the improvement in power as a function of number of visits and correlation between visits. It can also be applied in the optimization of experimental designs or usage of measuring devices. SHAVE is fast and easy to run, written in R and freely available online.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{di_pasquale_generation_2013,

title = {Generation of human cardiomyocytes: a differentiation protocol from feeder-free human induced pluripotent stem cells},

author = {Elisa {Di Pasquale} and Belle Song and Gianluigi Condorelli},

doi = {10.3791/50429},

issn = {1940-087X},

year  = {2013},

date = {2013-06-01},

journal = {Journal of Visualized Experiments: JoVE},

number = {76},

abstract = {In order to investigate the events driving heart development and to determine the molecular mechanisms leading to myocardial diseases in humans, it is essential first to generate functional human cardiomyocytes (CMs). The use of these cells in drug discovery and toxicology studies would also be highly beneficial, allowing new pharmacological molecules for the treatment of cardiac disorders to be validated pre-clinically on cells of human origin. Of the possible sources of CMs, induced pluripotent stem (iPS) cells are among the most promising, as they can be derived directly from readily accessible patient tissue and possess an intrinsic capacity to give rise to all cell types of the body (1). Several methods have been proposed for differentiating iPS cells into CMs, ranging from the classical embryoid bodies (EBs) aggregation approach to chemically defined protocols (2,3). In this article we propose an EBs-based protocol and show how this method can be employed to efficiently generate functional CM-like cells from feeder-free iPS cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23642048,

title = {Molecular changes induced by the curcumin analogue D6 in human melanoma cells},

author = {Rozzo, C. and Fanciulli, M. and Fraumene, C. and Corrias, A. and Cubeddu, T. and Sassu, I. and Cossu, S. and Nieddu, V. and Galleri, G. and Azara, E. and Dettori, M. A. and Fabbri, D. and Palmieri, G. and Pisano, M.},

year  = {2013},

date = {2013-05-01},

journal = {Mol Cancer},

volume = {12},

pages = {37},

abstract = {In a previous report, we described the in vitro and in vivo antiproliferative and proapoptotic activity of a hydroxylated biphenyl (D6), a structural analogue of curcumin, on malignant melanoma and neuroblastoma tumours. In this paper, we investigated the molecular changes induced by such a compound, underlying cell growth arrest and apoptosis in melanoma cells. To shed light on the mechanisms of action of D6, we firstly demonstrated its quick cellular uptake and subsequent block of cell cycle in G2/M phase transition. A gene expression profile analysis of D6-treated melanoma cells and fibroblasts was then carried out on high density microarrays, to assess gene expression changes induced by this compound. The expression profile study evidenced both an induction of stress response pathways and a modulation of cell growth regulation mechanisms. In particular, our data suggest that the antiproliferative and proapoptotic activities of D6 in melanoma could be partially driven by up-regulation of the p53 signalling pathways as well as by down-regulation of the PI3K/Akt and NF-kB pathways. Modulation of gene expression due to D6 treatment was verified by western blot analysis for single proteins of interest, confirming the results from the gene expression profile analysis. Our findings contribute to the understanding of the mechanisms of action of D6, through a comprehensive description of the molecular changes induced by this compound at the gene expression level, in agreement with the previously reported anti-tumour effects on melanoma cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{berndt_genome-wide_2013,

title = {Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture},

author = {Sonja I Berndt and Stefan Gustafsson and Reedik Mägi and Andrea Ganna and Eleanor Wheeler and Mary F Feitosa and ... and Joel N and Hirschhorn and Cecilia M Lindgren and Andrew P Morris and David Meyre and André Scherag and Mark I McCarthy and Elizabeth K Speliotes and Kari E North and Ruth J F Loos and Erik Ingelsson},

doi = {10.1038/ng.2606},

issn = {1546-1718},

year  = {2013},

date = {2013-05-01},

journal = {Nature Genetics},

volume = {45},

number = {5},

pages = {501--512},

abstract = {Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pangrazio_snx10_2013,

title = {SNX10 mutations define a subgroup of human autosomal recessive osteopetrosis with variable clinical severity},

author = {Alessandra Pangrazio and Anders Fasth and Andrea Sbardellati and Paul J Orchard and Kimberly A Kasow and Jamal Raza and Canan Albayrak and Davut Albayrak and Olivier M Vanakker and Barbara {De Moerloose} and Ashok Vellodi and Luigi D Notarangelo and Claire Schlack and Gabriele Strauss and J{ö}rn-Sven K{ü}hl and Elena Caldana and Nadia {Lo Iacono} and Lucia Susani and Uwe Kornak and Ansgar Schulz and Paolo Vezzoni and Anna Villa and Cristina Sobacchi},

doi = {10.1002/jbmr.1849},

issn = {1523-4681},

year  = {2013},

date = {2013-05-01},

journal = {Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research},

volume = {28},

number = {5},

pages = {1041--1049},

abstract = {Human Autosomal Recessive Osteopetrosis (ARO) is a genetically heterogeneous disorder caused by reduced bone resorption by osteoclasts. In 2000, we found that mutations in the TCIRG1 gene encoding for a subunit of the proton pump (V-ATPase) are responsible for more than one-half of ARO cases. Since then, five additional genes have been demonstrated to be involved in the pathogenesis of the disease, leaving approximately 25% of cases that could not be associated with a genotype. Very recently, a mutation in the sorting nexin 10 (SNX10) gene, whose product is suggested to interact with the proton pump, has been found in 3 consanguineous families of Palestinian origin, thus adding a new candidate gene in patients not previously classified. Here we report the identification of 9 novel mutations in this gene in 14 ARO patients from 12 unrelated families of different geographic origin. Interestingly, we define the molecular defect in three cases of "Västerbottenian osteopetrosis," named for the Swedish Province where a higher incidence of the disease has been reported. In our cohort of more than 310 patients from all over the world, SNX10-dependent ARO constitutes 4% of the cases, with a frequency comparable to the receptor activator of NF-κB ligand (RANKL), receptor activator of NF-κB (RANK) and osteopetrosis-associated transmembrane protein 1 (OSTM1)-dependent subsets. Although the clinical presentation is relatively variable in severity, bone seems to be the only affected tissue and the defect can be almost completely rescued by hematopoietic stem cell transplantation (HSCT). These results confirm the involvement of the SNX10 gene in human ARO and identify a new subset with a relatively favorable prognosis as compared to TCIRG1-dependent cases. Further analyses will help to better understand the role of SNX10 in osteoclast physiology and verify whether this protein might be considered a new target for selective antiresorptive therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hek_genome-wide_2013,

title = {A genome-wide association study of depressive symptoms.},

author = {Hek, Karin and Demirkan, Ayse and Lahti, Jari and Terracciano, Antonio and Teumer, Alexander and Cornelis, Marilyn C. and Amin, Najaf and Bakshis, Erin and Baumert, Jens and Ding, Jingzhong and Liu, Yongmei and Marciante, Kristin and Meirelles, Osorio and Nalls, Michael A. and Sun, Yan V. and Vogelzangs, Nicole and Yu, Lei and Bandinelli, Stefania and Benjamin, Emelia J. and Bennett, David A. and Boomsma, Dorret and Cannas, Alessandra and Coker, Laura H. and de Geus, Eco and De Jager, Philip L. and Diez-Roux, Ana V. and Purcell, Shaun and Hu, Frank B. and Rimma, Eric B. and Hunter, David J. and Jensen, Majken K. and Curhan, Gary and Rice, Kenneth and Penman, Alan D. and Rotter, Jerome I. and Sotoodehnia, Nona and Emeny, Rebecca and Eriksson, Johan G. and Evans, Denis A. and Ferrucci, Luigi and Fornage, Myriam and Gudnason, Vilmundur and Hofman, Albert and Illig, Thomas and Kardia, Sharon and Kelly-Hayes, Margaret and Koenen, Karestan and Kraft, Peter and Kuningas, Maris and Massaro, Joseph M. and Melzer, David and Mulas, Antonella and Mulder, Cornelis L. and Murray, Anna and Oostra, Ben A. and Palotie, Aarno and Penninx, Brenda and Petersmann, Astrid and Pilling, Luke C. and Psaty, Bruce and Rawal, Rajesh and Reiman, Eric M. and Schulz, Andrea and Shulman, Joshua M. and Singleton, Andrew B. and Smith, Albert V. and Sutin, Angelina R. and Uitterlinden, Andre G. and Volzke, Henry and Widen, Elisabeth and Yaffe, Kristine and Zonderman, Alan B. and Cucca, Francesco and Harris, Tamara and Ladwig, Karl-Heinz and Llewellyn, David J. and Raikkonen, Katri and Tanaka, Toshiko and van Duijn, Cornelia M. and Grabe, Hans J. and Launer, Lenore J. and Lunetta, Kathryn L. and Mosley, Thomas H. Jr and Newman, Anne B. and Tiemeier, Henning and Murabito, Joanne},

doi = {10.1016/j.biopsych.2012.09.033},

issn = {1873-2402 0006-3223},

year  = {2013},

date = {2013-04-01},

journal = {Biol Psychiatry},

volume = {73},

number = {7},

pages = {667--678},

abstract = {BACKGROUND: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. METHODS: In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (ptextless1x10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. RESULTS: The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05x10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ramos_macrophages_2013,

title = {Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia},

author = {Pedro Ramos and Carla Casu and Sara Gardenghi and Laura Breda and Bart J Crielaard and Ella Guy and Maria Franca Marongiu and Ritama Gupta and Ross L Levine and Omar Abdel-Wahab and Benjamin L Ebert and Nico {Van Rooijen} and Saghi Ghaffari and Robert W Grady and Patricia J Giardina and Stefano Rivella},

doi = {10.1038/nm.3126},

issn = {1546-170X},

year  = {2013},

date = {2013-04-01},

journal = {Nature Medicine},

volume = {19},

number = {4},

pages = {437--445},

abstract = {Regulation of erythropoiesis is achieved by the integration of distinct signals. Among them, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages to physiological and pathological conditions of enhanced erythropoiesis. We used mouse models of induced anemia, polycythemia vera and β-thalassemia in which macrophages were chemically depleted. Our data indicate that macrophages contribute decisively to recovery from induced anemia, as well as the pathological progression of polycythemia vera and β-thalassemia, by modulating erythroid proliferation and differentiation. We validated these observations in primary human cultures, showing a direct impact of macrophages on the proliferation and enucleation of erythroblasts from healthy individuals and patients with polycythemia vera or β-thalassemia. The contribution of macrophages to stress and pathological erythropoiesis, which we have termed stress erythropoiesis macrophage-supporting activity, may have therapeutic implications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23337808,

title = {Wiskott-Aldrich syndrome protein-mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells},

author = {F Prete and M Catucci and M Labrada and S Gobessi and M C Castiello and E Bonomi and A Aiuti and W Vermi and C Cancrini and A Metin and S Hambleton and R Bredius and L D Notarangelo and M van der Burg and U Kalinke and A Villa and F Benvenuti},

year  = {2013},

date = {2013-02-01},

journal = {J Exp Med},

volume = {210},

number = {2},

pages = {355--374},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23239471,

title = {Ŧhe impairment of ĦCCS leads to MLS syndrome by activating a non-canonical cell death pathway in the brain and eyes},

author = {A Indrieri and I Conte and G Chesi and A Romano and J Quartararo and R Tatè and D Ghezzi and M Zeviani and P Goffrini and I Ferrero and P Bovolenta and B Franco},

year  = {2013},

date = {2013-02-01},

journal = {EMBO Mol Med},

volume = {5},

number = {2},

pages = {280--293},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kottgen_genome-wide_2013,

title = {Genome-wide association analyses identify 18 new loci associated with serum urate concentrations},

author = {K{ö}ttgen, Anna and Albrecht, Eva and Teumer, Alexander and Vitart, Veronique and Krumsiek, Jan and Hundertmark, Claudia and Pistis, Giorgio and Ruggiero, Daniela and ... and Tore, Silvia and ... and Ripatti, Samuli and Soranzo, Nicole and Toniolo, Daniela and Chasman, Daniel I and Raitakari, Olli and Kao, W H Linda and Ciullo, Marina and Fox, Caroline S and Caulfield, Mark and Bochud, Murielle and Gieger, Christian},

doi = {10.1038/ng.2500},

issn = {1546-1718},

year  = {2013},

date = {2013-02-01},

urldate = {2013-02-01},

journal = {Nature Genetics},

volume = {45},

number = {2},

pages = {145--154},

abstract = {Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23845947b,

title = {Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome},

year  = {2013},

date = {2013-01-01},

journal = {Science},

volume = {341},

number = {6148},

pages = {1233151},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23167636,

title = {Cytogenetic analysis of human cells reveals specific patterns of ĐNA damage in replicative and oncogene-induced senescence},

author = {G Falcone and A Mazzola and F Michelini and G Bossi and F Censi and M G Biferi and L Minghetti and G Floridia and M Federico and A Musio and M Crescenzi},

year  = {2013},

date = {2013-01-01},

volume = {12},

number = {2},

pages = {312--315},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23463027,

title = {Đoubly heterozygous LMNA and ŦŦN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy},

author = {R Roncarati and C Viviani Anselmi and P Krawitz and G Lattanzi and Y von Kodolitsch and A Perrot and E di Pasquale and L Papa and P Portararo and M Columbaro and A Forni and G Faggian and G Condorelli and P N Robinson},

year  = {2013},

date = {2013-01-01},

journal = {Eur J Hum Genet},

volume = {21},

number = {10},

pages = {1105--1111},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23845947,

title = {Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome},

year  = {2013},

date = {2013-01-01},

journal = {Science},

volume = {341},

number = {6148},

pages = {1233151},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23922949,

title = {MicroRNA-1 downregulation increases connexin 43 displacement and induces ventricular tachyarrhythmias in rodent hypertrophic hearts},

author = {A Curcio and D Torella and C Iaconetti and E Pasceri and J Sabatino and S Sorrentino and S Giampà and M Micieli and A Polimeni and B J Henning and A Leone and D Catalucci and G M Ellison and G Condorelli and C Indolfi},

year  = {2013},

date = {2013-01-01},

journal = {PLoS One},

volume = {8},

number = {7},

pages = {e70158},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rietveld_gwas_2013,

title = {GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.},

author = {Rietveld, Cornelius A. and Medland, Sarah E. and Derringer, Jaime and Yang, Jian and Esko, Tonu and Martin, Nicolas W. and Westra, Harm-Jan and Shakhbazov, Konstantin and [...] and Cucca, Francesco and de Andrade, Mariza and De Jager, Philip L. and De Neve, Jan-Emmanuel and Deary, Ian J. and Dedoussis, George V. and Deloukas, Panos and Dimitriou, Maria and Eiriksdottir, Guethny and Elderson, Martin F. and Eriksson, Johan G. and Evans, David M. and Faul, Jessica D. and Ferrucci, Luigi and Garcia, Melissa E. and Gronberg, Henrik and Guethnason, Vilmundur and Hall, Per and Harris, Juliette M. and Harris, Tamara B. and Hastie, Nicholas D. and Heath, Andrew C. and Hernandez, Dena G. and Hoffmann, Wolfgang and Hofman, Adriaan and Holle, Rolf and Holliday, Elizabeth G. and Hottenga, Jouke-Jan and Iacono, William G. and Illig, Thomas and Jarvelin, Marjo-Riitta and Kahonen, Mika and Kaprio, Jaakko and Kirkpatrick, Robert M. and Kowgier, Matthew and Latvala, Antti and Launer, Lenore J. and Lawlor, Debbie A. and Lehtimaki, Terho and Li, Jingmei and Lichtenstein, Paul and Lichtner, Peter and Liewald, David C. and Madden, Pamela A. and Magnusson, Patrik K. E. and Makinen, Tomi E. and Masala, Marco and McGue, Matt and Metspalu, Andres and Mielck, Andreas and Miller, Michael B. and Montgomery, Grant W. and Mukherjee, Sutapa and Nyholt, Dale R. and Oostra, Ben A. and Palmer, Lyle J. and Palotie, Aarno and Penninx, Brenda W. J. H. and Perola, Markus and Peyser, Patricia A. and Preisig, Martin and Raikkonen, Katri and Raitakari, Olli T. and Realo, Anu and Ring, Susan M. and Ripatti, Samuli and Rivadeneira, Fernando and Rudan, Igor and Rustichini, Aldo and Salomaa, Veikko and Sarin, Antti-Pekka and Schlessinger, David and Scott, Rodney J. and Snieder, Harold and St Pourcain, Beate and Starr, John M. and Sul, Jae Hoon and Surakka, Ida and Svento, Rauli and Teumer, Alexander and Tiemeier, Henning and van Rooij, Frank J. A. and Van Wagoner, David R. and Vartiainen, Erkki and Viikari, Jorma and Vollenweider, Peter and Vonk, Judith M. and Waeber, Gerard and Weir, David R. and Wichmann, H.-Erich and Widen, Elisabeth and Willemsen, Gonneke and Wilson, James F. and Wright, Alan F. and Conley, Dalton and Davey-Smith, George and Franke, Lude and Groenen, Patrick J. F. and Hofman, Albert and Johannesson, Magnus and Kardia, Sharon L. R. and Krueger, Robert F. and Laibson, David and Martin, Nicholas G. and Meyer, Michelle N. and Posthuma, Danielle and Thurik, A. Roy and Timpson, Nicholas J. and Uitterlinden, Andre G. and van Duijn, Cornelia M. and Visscher, Peter M. and Benjamin, Daniel J. and Cesarini, David and Koellinger, Philipp D.},

doi = {10.1126/science.1235488},

issn = {1095-9203 0036-8075},

year  = {2013},

date = {2013-01-01},

journal = {Science},

volume = {340},

number = {6139},

pages = {1467--1471},

abstract = {A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) approximately 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for approximately 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{van_der_loos_molecular_2013,

title = {The molecular genetic architecture of self-employment.},

author = {van der Loos, Matthijs J. H. M. and Rietveld, Cornelius A. and Eklund, Niina and Koellinger, Philipp D. and Rivadeneira, Fernando and Abecasis, Goncalo R. and Ankra-Badu, Georgina A. and Baumeister, Sebastian E. and Benjamin, Daniel J. and Biffar, Reiner and Blankenberg, Stefan and Boomsma, Dorret I. and Cesarini, David and Cucca, Francesco and de Geus, Eco J. C. and Dedoussis, George and Deloukas, Panos and Dimitriou, Maria and Eiriksdottir, Guethny and Eriksson, Johan and Gieger, Christian and Gudnason, Vilmundur and Hohne, Birgit and Holle, Rolf and Hottenga, Jouke-Jan and Isaacs, Aaron and Jarvelin, Marjo-Riitta and Johannesson, Magnus and Kaakinen, Marika and Kahonen, Mika and Kanoni, Stavroula and Laaksonen, Maarit A. and Lahti, Jari and Launer, Lenore J. and Lehtimaki, Terho and Loitfelder, Marisa and Magnusson, Patrik K. E. and Naitza, Silvia and Oostra, Ben A. and Perola, Markus and Petrovic, Katja and Quaye, Lydia and Raitakari, Olli and Ripatti, Samuli and Scheet, Paul and Schlessinger, David and Schmidt, Carsten O. and Schmidt, Helena and Schmidt, Reinhold and Senft, Andrea and Smith, Albert V. and Spector, Timothy D. and Surakka, Ida and Svento, Rauli and Terracciano, Antonio and Tikkanen, Emmi and van Duijn, Cornelia M. and Viikari, Jorma and Volzke, Henry and Wichmann, H.-Erich and Wild, Philipp S. and Willems, Sara M. and Willemsen, Gonneke and van Rooij, Frank J. A. and Groenen, Patrick J. F. and Uitterlinden, Andre G. and Hofman, Albert and Thurik, A. Roy},

doi = {10.1371/journal.pone.0060542},

issn = {1932-6203 1932-6203},

year  = {2013},

date = {2013-01-01},

journal = {PLoS One},

volume = {8},

number = {4},

pages = {e60542},

abstract = {Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (sigma(g)(2)/sigma(P)(2) = 25%, h(2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with ptextless10(-5) were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (ptextgreater/=0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pippucci_novel_2013,

title = {A novel null homozygous mutation confirms CACNA2D2 as a gene mutated in epileptic encephalopathy.},

author = {Pippucci, Tommaso and Parmeggiani, Antonia and Palombo, Flavia and Maresca, Alessandra and Angius, Andrea and Crisponi, Laura and Cucca, Francesco and Liguori, Rocco and Valentino, Maria Lucia and Seri, Marco and Carelli, Valerio},

doi = {10.1371/journal.pone.0082154},

issn = {1932-6203 1932-6203},

year  = {2013},

date = {2013-01-01},

journal = {PLoS One},

volume = {8},

number = {12},

pages = {e82154},

abstract = {Contribution to epileptic encephalopathy (EE) of mutations in CACNA2D2, encoding alpha2delta-2 subunit of Voltage Dependent Calcium Channels, is unclear. To date only one CACNA2D2 mutation altering channel functionality has been identified in a single family. In the same family, a rare CELSR3 polymorphism also segregated with disease. Involvement of CACNA2D2 in EE is therefore not confirmed, while that of CELSR3 is questionable. In a patient with epilepsy, dyskinesia, cerebellar atrophy, psychomotor delay and dysmorphic features, offspring to consanguineous parents, we performed whole exome sequencing (WES) for homozygosity mapping and mutation detection. WES identified extended autozygosity on chromosome 3, containing two novel homozygous candidate mutations: c.1295delA (p.Asn432fs) in CACNA2D2 and c.G6407A (p.Gly2136Asp) in CELSR3. Gene prioritization pointed to CACNA2D2 as the most prominent candidate gene. The WES finding in CACNA2D2 resulted to be statistically significant (p = 0.032), unlike that in CELSR3. CACNA2D2 homozygous c.1295delA essentially abolished alpha2delta-2 expression. In summary, we identified a novel null CACNA2D2 mutation associated to a clinical phenotype strikingly similar to the Cacna2d2 null mouse model. Molecular and statistical analyses together argued in favor of a causal contribution of CACNA2D2 mutations to EE, while suggested that finding in CELSR3, although potentially damaging, is likely incidental.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{porcu_meta-analysis_2013,

title = {A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.},

author = {Porcu, Eleonora and Medici, Marco and Pistis, Giorgio and Volpato, Claudia B. and Wilson, Scott G. and Cappola, Anne R. and Bos, Steffan D. and Deelen, Joris and den Heijer, Martin and Freathy, Rachel M. and Lahti, Jari and Liu, Chunyu and Lopez, Lorna M. and Nolte, Ilja M. and O'Connell, Jeffrey R. and Tanaka, Toshiko and Trompet, Stella and Arnold, Alice and Bandinelli, Stefania and Beekman, Marian and Bohringer, Stefan and Brown, Suzanne J. and Buckley, Brendan M. and Camaschella, Clara and de Craen, Anton J. M. and Davies, Gail and de Visser, Marieke C. H. and Ford, Ian and Forsen, Tom and Frayling, Timothy M. and Fugazzola, Laura and Gogele, Martin and Hattersley, Andrew T. and Hermus, Ad R. and Hofman, Albert and Houwing-Duistermaat, Jeanine J. and Jensen, Richard A. and Kajantie, Eero and Kloppenburg, Margreet and Lim, Ee M. and Masciullo, Corrado and Mariotti, Stefano and Minelli, Cosetta and Mitchell, Braxton D. and Nagaraja, Ramaiah and Netea-Maier, Romana T. and Palotie, Aarno and Persani, Luca and Piras, Maria G. and Psaty, Bruce M. and Raikkonen, Katri and Richards, J. Brent and Rivadeneira, Fernando and Sala, Cinzia and Sabra, Mona M. and Sattar, Naveed and Shields, Beverley M. and Soranzo, Nicole and Starr, John M. and Stott, David J. and Sweep, Fred C. G. J. and Usala, Gianluca and van der Klauw, Melanie M. and van Heemst, Diana and van Mullem, Alies and Vermeulen, Sita H. and Visser, W. Edward and Walsh, John P. and Westendorp, Rudi G. J. and Widen, Elisabeth and Zhai, Guangju and Cucca, Francesco and Deary, Ian J. and Eriksson, Johan G. and Ferrucci, Luigi and Fox, Caroline S. and Jukema, J. Wouter and Kiemeney, Lambertus A. and Pramstaller, Peter P. and Schlessinger, David and Shuldiner, Alan R. and Slagboom, Eline P. and Uitterlinden, Andre G. and Vaidya, Bijay and Visser, Theo J. and Wolffenbuttel, Bruce H. R. and Meulenbelt, Ingrid and Rotter, Jerome I. and Spector, Tim D. and Hicks, Andrew A. and Toniolo, Daniela and Sanna, Serena and Peeters, Robin P. and Naitza, Silvia},

doi = {10.1371/journal.pgen.1003266},

issn = {1553-7404 1553-7390},

year  = {2013},

date = {2013-01-01},

journal = {PLoS Genet},

volume = {9},

number = {2},

pages = {e1003266},

abstract = {Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{elhaik_genochip:_2013,

title = {The GenoChip: a new tool for genetic anthropology.},

author = {Elhaik, Eran and Greenspan, Elliott and Staats, Sean and Krahn, Thomas and Tyler-Smith, Chris and Xue, Yali and Tofanelli, Sergio and Francalacci, Paolo and Cucca, Francesco and Pagani, Luca and Jin, Li and Li, Hui and Schurr, Theodore G. and Greenspan, Bennett and Spencer Wells, R.},

doi = {10.1093/gbe/evt066},

issn = {1759-6653 1759-6653},

year  = {2013},

date = {2013-01-01},

journal = {Genome Biol Evol},

volume = {5},

number = {5},

pages = {1021--1031},

abstract = {The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project's new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. The GenoChip includes ancestry informative markers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all known Y-chromosome and mtDNA haplogroups. The chip was carefully vetted to avoid inclusion of medically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs without any known health, medical, or phenotypic relevance, the GenoChip is a useful tool for genetic anthropology and population genetics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{yokoyama_mll_2013,

title = {MLL becomes functional through intra-molecular interaction not by proteolytic processing},

author = {Akihiko Yokoyama and Francesca Ficara and Mark J Murphy and Christian Meisel and Chikako Hatanaka and Issay Kitabayashi and Michael L Cleary},

doi = {10.1371/journal.pone.0073649},

issn = {1932-6203},

year  = {2013},

date = {2013-01-01},

journal = {PloS One},

volume = {8},

number = {9},

pages = {e73649},

abstract = {The mixed lineage leukemia (MLL) protein is an epigenetic transcriptional regulator that controls proliferative expansion of immature hematopoietic progenitors, whose aberrant activation triggers leukemogenesis. A mature MLL protein is produced by formation of an intra-molecular complex and proteolytic cleavage. However the biological significance of these two post-transcriptional events remains unclear. To address their in vivo roles, mouse mutant alleles were created that exclusively express either a variant protein incapable of intra-molecular interaction (designated de) or an uncleavable mutant protein (designated uc). The de homozygous mice died during midgestation and manifested devastating failure in embryonic development and reduced numbers of hematopoietic progenitors, whereas uc homozygous mice displayed no apparent defects. Expression of MLL target genes was severely impaired in de homozygous fibroblasts but unaffected in uc homozygous fibroblasts. These results unequivocally demonstrate that intra-molecular complex formation is a crucial maturation step whereas proteolytic cleavage is dispensable for MLL-dependent gene activation and proliferation in vivo.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{varrone_circulating_2013,

title = {The circulating level of FABP3 is an indirect biomarker of microRNA-1},

author = {Francesca Varrone and Barbara Gargano and Pierluigi Carullo and Dario {Di Silvestre} and Antonella {De Palma} and Ludovica Grasso and Carolina {Di Somma} and Pierluigi Mauri and Louise Benazzi and Anna Franzone and Gloria Saccani Jotti and Marie-Louise Bang and Giovanni Esposito and Annamaria Colao and Gianluigi Condorelli and Daniele Catalucci},

doi = {10.1016/j.jacc.2012.08.1003},

issn = {1558-3597},

year  = {2013},

date = {2013-01-01},

journal = {Journal of the American College of Cardiology},

volume = {61},

number = {1},

pages = {88--95},

abstract = {OBJECTIVES: This study sought to identify proteins from the cardiomyocyte (CM) secretome that are directly targeted by the muscle-specific microRNA-1 (miR-1), and thus reflect the pathophysiological state of the CM. 

BACKGROUND: MicroRNAs play critical regulatory roles during myocardial remodeling and progression to heart failure. However, it remains unknown whether secreted microRNA-targeted proteins can be used as indicators of myocardial microRNA expression and function. 

METHODS: A proteomic analysis based on multidimensional protein identification technology was performed on supernatants from cultured CMs overexpressing miR-1. Biochemical assays and an inducible cardiac-specific transgenic mouse model overexpressing miR-1 were used to demonstrate that heart-type fatty acid-binding protein-3 (FABP3) is a target of miR-1. Levels of miR-1 and FABP3 in cardiac tissue and plasma samples from mouse models as well as human patients were quantified by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The study included wild-type mice subjected to ventricular pressure overload or fasting, as well as patients diagnosed with ventricular hypertrophy due to valvular aortic stenosis, acromegaly, or growth hormone deficiency, conditions associated with altered miR-1 expression. 

RESULTS: An inverse relationship between myocardial expression of miR-1 and circulating levels of FABP3 was found both in vitro and in vivo under various pathological conditions. 

CONCLUSIONS: Assessment of FABP3 plasma levels in human patients might be used for indirectly measuring cardiac miR-1 activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{priori_induced_2013,

title = {Induced pluripotent stem cell-derived cardiomyocytes in studies of inherited arrhythmias},

author = {Silvia G Priori and Carlo Napolitano and Elisa {Di Pasquale} and Gianluigi Condorelli},

doi = {10.1172/JCI62838},

issn = {1558-8238},

year  = {2013},

date = {2013-01-01},

journal = {The Journal of Clinical Investigation},

volume = {123},

number = {1},

pages = {84--91},

abstract = {The discovery of the genetic basis of inherited arrhythmias has paved the way for an improved understanding of arrhythmogenesis in a wide spectrum of life-threatening conditions. In vitro expression of mutations and transgenic animal models have been instrumental in enhancing this understanding, but the applicability of results to the human heart remains unknown. The ability to differentiate induced pluripotent stem cells (iPSs) into cardiomyocytes enables the potential to generate patient-specific myocytes, which could be used to recapitulate the features of inherited arrhythmias in the context of the patient's genetic background. Few studies have been reported on iPS-derived myocytes obtained from patients with heritable arrhythmias, but they have demonstrated the applicability of this innovative approach to the study of inherited arrhythmias. Here we review the results achieved by iPS investigations in arrhythmogenic syndromes and discuss the existing challenges to be addressed before the use of iPS-derived myocytes can become a part of personalized management of inherited arrhythmias.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}