Fabio Busonero

@article{danjou_genome-wide_2015,

title = {Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels},

author = {Fabrice Danjou and Magdalena Zoledziewska and Carlo Sidore and Maristella Steri and Fabio Busonero and Andrea Maschio and Antonella Mulas and Lucia Perseu and Susanna Barella and Eleonora Porcu and Giorgio Pistis and Maristella Pitzalis and Mauro Pala and Stephan Menzel and Sarah Metrustry and Timothy D Spector and Lidia Leoni and Andrea Angius and Manuela Uda and Paolo Moi and Swee Lay Thein and Renzo Galanello and Gon{ç}alo R Abecasis and David Schlessinger and Serena Sanna and Francesco Cucca},

doi = {10.1038/ng.3307},

issn = {1546-1718},

year  = {2015},

date = {2015-11-01},

journal = {Nature Genetics},

volume = {47},

number = {11},

pages = {1264--1271},

abstract = {We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sidore_genome_2015,

title = {Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers},

author = {Carlo Sidore and Fabio Busonero and Andrea Maschio and Eleonora Porcu and Silvia Naitza and Magdalena Zoledziewska and Antonella Mulas and Giorgio Pistis and Maristella Steri and Fabrice Danjou and Alan Kwong and Vicente Diego {Ortega Del Vecchyo} and Charleston W K Chiang and Jennifer Bragg-Gresham and Maristella Pitzalis and Ramaiah Nagaraja and Brendan Tarrier and Christine Brennan and Sergio Uzzau and Christian Fuchsberger and Rossano Atzeni and Frederic Reinier and Riccardo Berutti and Jie Huang and Nicholas J Timpson and Daniela Toniolo and Paolo Gasparini and Giovanni Malerba and George Dedoussis and Eleftheria Zeggini and Nicole Soranzo and Chris Jones and Robert Lyons and Andrea Angius and Hyun M Kang and John Novembre and Serena Sanna and David Schlessinger and Francesco Cucca and Gon{ç}alo R Abecasis},

doi = {10.1038/ng.3368},

issn = {1546-1718},

year  = {2015},

date = {2015-11-01},

journal = {Nature Genetics},

volume = {47},

number = {11},

pages = {1272--1281},

abstract = {We report ∼17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, ∼76,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population.},

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{1000_genomes_project_consortium_integrated_2012,

title = {An integrated map of genetic variation from 1,092 human genomes},

author = {1000 Genomes Project Consortium and Goncalo R Abecasis and Adam Auton and Lisa D Brooks and Mark A DePristo and Richard M Durbin and Robert E Handsaker and Hyun Min Kang and Gabor T Marth and Gil A McVean},

doi = {10.1038/nature11632},

issn = {1476-4687},

year  = {2012},

date = {2012-11-01},

journal = {Nature},

volume = {491},

number = {7422},

pages = {56--65},

abstract = {By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sanna_common_2009,

title = {Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia},

author = {Serena Sanna and Fabio Busonero and Andrea Maschio and Patrick F McArdle and Gianluca Usala and Mariano Dei and Sandra Lai and Antonella Mulas and Maria Grazia Piras and Lucia Perseu and Marco Masala and Mara Marongiu and Laura Crisponi and Silvia Naitza and Renzo Galanello and Gon{ç}alo R Abecasis and Alan R Shuldiner and David Schlessinger and Antonio Cao and Manuela Uda},

doi = {10.1093/hmg/ddp203},

issn = {1460-2083},

year  = {2009},

date = {2009-07-01},

journal = {Human Molecular Genetics},

volume = {18},

number = {14},

pages = {2711--2718},

abstract = {Bilirubin, resulting largely from the turnover of hemoglobin, is found in the plasma in two main forms: unconjugated or conjugated with glucuronic acid. Unconjugated bilirubin is transported into hepatocytes. There, it is glucuronidated by UGT1A1 and secreted into the bile canaliculi. We report a genome wide association scan in 4300 Sardinian individuals for total serum bilirubin levels. In addition to the two known loci previously involved in the regulation of bilirubin levels, UGT1A1 (P = 6.2 x 10(-62)) and G6PD (P = 2.5 x 10(-8)), we observed a strong association on chromosome 12 within the SLCO1B3 gene (P = 3.9 x 10(-9)). Our findings were replicated in an independent sample of 1860 Sardinians and in 832 subjects from the Old Order Amish (combined P textless 5 x 10(-14)). We also show that SLC01B3 variants contribute to idiopathic mild unconjugated hyperbilirubinemia. Thus, SLC01B3 appears to be involved in the regulation of serum bilirubin levels in healthy individuals and in some bilirubin-related disorders that are only partially explained by other known gene variants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}