Daniela Zanetti
Researcher
Area of interest:
My long-term goal is to use the power of population genetics, epidemiology, and Mendelian Randomization to define the possible causal genes involved in the development of complex traits. My academic training and research experience have provided me with an excellent background in multiple biological disciplines including biology, population genetics, epidemiology, and genetics.
During my PhD research at the University of Barcelona, I have identified cardiovascular genetic risk markers in populations of different ancestry, and natural selection patterns involved in cardiovascular risk loci. In my postdoctoral training at Stanford, applying Mendelian Randomization methods, I have identified causal genetic mechanisms involved in the development of cardiometabolic traits, such as low birth weight and kidney function. In addition, I am currently working on a project involving proteomic data to predict insulin sensitivity.
Currently at the IRGB-CNR, I will study the genetic and molecular components that differentially impact men and women on cardiometabolic traits. My project funded by the Marie Curie Postdoctoral Fellow will lead to find new drug target to perform equally well in males and females and will open the door to improve personalized and precision medicine in the near future.
A complete list of my published work can be found here
Most significant publications:
2022
Selle, J.; Dinger, K.; Jentgen, V.; Zanetti, D.; Will, J.; Georgomanolis, T.; Vohlen, C.; Wilke, R.; Kojonazarov, B.; Klymenko, O.; Mohr, J.; Koningsbruggen-Rietschel, S. V; Rhodes, C. J.; Ulrich, A.; Hirani, D.; Nestler, T.; Odenthal, M.; Mahabir, E.; Nayakanti, S.; Dabral, S.; Wunderlich, T.; Priest, J.; Seeger, W.; tsch, J.; Pullamsetti, S. S.; Alcazar, M. A. Alejandre
Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life Journal Article
In: Nat Commun, 13 (1), pp. 4352, 2022.
@article{pmid35896539,
title = {Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life},
author = {J. Selle and K. Dinger and V. Jentgen and D. Zanetti and J. Will and T. Georgomanolis and C. Vohlen and R. Wilke and B. Kojonazarov and O. Klymenko and J. Mohr and S. V Koningsbruggen-Rietschel and C. J. Rhodes and A. Ulrich and D. Hirani and T. Nestler and M. Odenthal and E. Mahabir and S. Nayakanti and S. Dabral and T. Wunderlich and J. Priest and W. Seeger and J. tsch and S. S. Pullamsetti and M. A. Alejandre Alcazar},
year = {2022},
date = {2022-07-01},
journal = {Nat Commun},
volume = {13},
number = {1},
pages = {4352},
abstract = {s/forced vital capacity ratio Z-score (used as proxy for lung function) and asthma. We conclude that the interleukin-6-FoxO1 pathway in SMC is a molecular mechanism by which perinatal obesity programs the bronchial and vascular structure and function, thereby driving CLD development. Thus, FoxO1 reconstitution provides a potential therapeutic option for preventing this metabolic programming of CLD.},
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s/forced vital capacity ratio Z-score (used as proxy for lung function) and asthma. We conclude that the interleukin-6-FoxO1 pathway in SMC is a molecular mechanism by which perinatal obesity programs the bronchial and vascular structure and function, thereby driving CLD development. Thus, FoxO1 reconstitution provides a potential therapeutic option for preventing this metabolic programming of CLD.
2021
Lind, L.; Zanetti, D.; Ingelsson, M.; Gustafsson, S.; v, J.; Assimes, T. L.
Large-Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Ħeart Failure Journal Article
In: J Am Heart Assoc, 10 (23), pp. e023330, 2021.
@article{pmid34845919,
title = {Large-Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Ħeart Failure},
author = {L. Lind and D. Zanetti and M. Ingelsson and S. Gustafsson and J. v and T. L. Assimes},
year = {2021},
date = {2021-12-01},
journal = {J Am Heart Assoc},
volume = {10},
number = {23},
pages = {e023330},
abstract = {=0.0038). Conclusions Large-scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.},
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=0.0038). Conclusions Large-scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.
2020
Zanetti, D.; Gustafsson, S.; Assimes, T. L.; Ingelsson, E.
Comprehensive Investigation of Circulating Biomarkers and Ŧheir Causal Role in Atherosclerosis-Related Risk Factors and Clinical Events Journal Article
In: Circ Genom Precis Med, 13 (6), pp. e002996, 2020.
@article{pmid33125266,
title = {Comprehensive Investigation of Circulating Biomarkers and Ŧheir Causal Role in Atherosclerosis-Related Risk Factors and Clinical Events},
author = {D. Zanetti and S. Gustafsson and T. L. Assimes and E. Ingelsson},
year = {2020},
date = {2020-12-01},
journal = {Circ Genom Precis Med},
volume = {13},
number = {6},
pages = {e002996},
abstract = {Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood. 933 participants of the UK Biobank. ). Our results suggest that it is unlikely that CRP (C-reactive protein) and vitamin D play causal roles of any meaningful magnitude in development of cardiometabolic disease. We confirmed and extended known associations and reported several novel causal associations providing important insights about the cause of these diseases, which can help accelerate new prevention strategies.},
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Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood. 933 participants of the UK Biobank. ). Our results suggest that it is unlikely that CRP (C-reactive protein) and vitamin D play causal roles of any meaningful magnitude in development of cardiometabolic disease. We confirmed and extended known associations and reported several novel causal associations providing important insights about the cause of these diseases, which can help accelerate new prevention strategies.
Zanetti, D.; Bergman, H.; Burgess, S.; Assimes, T. L.; Bhalla, V.; Ingelsson, E.
Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank: Observational and Mendelian Randomization Analyses Journal Article
In: Hypertension, 75 (3), pp. 714–722, 2020.
@article{pmid32008434,
title = {Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank: Observational and Mendelian Randomization Analyses},
author = {D. Zanetti and H. Bergman and S. Burgess and T. L. Assimes and V. Bhalla and E. Ingelsson},
year = {2020},
date = {2020-03-01},
journal = {Hypertension},
volume = {75},
number = {3},
pages = {714--722},
abstract = {=0.02). Our comprehensive study of urinary biomarkers performed using state-of-the-art analyses of causality mirror and extend findings from randomized interventional trials which have established UNa/UK as a risk factor for hypertension. In addition, we detect a causal feedback loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.},
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=0.02). Our comprehensive study of urinary biomarkers performed using state-of-the-art analyses of causality mirror and extend findings from randomized interventional trials which have established UNa/UK as a risk factor for hypertension. In addition, we detect a causal feedback loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.
2019
Zanetti, D.; Rao, A.; Gustafsson, S.; Assimes, T. L.; Montgomery, S. B.; Ingelsson, E.
potassium excretion Journal Article
In: Kidney Int, 95 (5), pp. 1197–1208, 2019.
@article{pmid30910378,
title = {potassium excretion},
author = {D. Zanetti and A. Rao and S. Gustafsson and T. L. Assimes and S. B. Montgomery and E. Ingelsson},
year = {2019},
date = {2019-05-01},
journal = {Kidney Int},
volume = {95},
number = {5},
pages = {1197--1208},
abstract = {Urine biomarkers reflecting kidney function and handling of dietary sodium and potassium are strongly associated with several common diseases including chronic kidney disease, cardiovascular disease, and diabetes mellitus. Knowledge about the genetic determinants of these biomarkers may shed light on pathophysiological mechanisms underlying the development of these diseases. We performed genome-wide association studies of urinary albumin: creatinine ratio (UACR), urinary potassium: creatinine ratio (UK/UCr), urinary sodium: creatinine ratio (UNa/UCr) and urinary sodium: potassium ratio (UNa/UK) in up to 218,450 (discovery) and 109,166 (replication) unrelated individuals of European ancestry from the UK Biobank. Further, we explored genetic correlations, tissue-specific gene expression, and possible genes implicated in the regulation of these biomarkers. After replication, we identified 19 genome-wide significant independent loci associated with UACR, 6 each with UK/UCr and UNa/UCr, and 4 with UNa/UK. In addition to 22 novel associations, we confirmed several established associations, including between the CUBN locus and microalbuminuria. We detected high pairwise genetic correlation across the urinary biomarkers, and between their levels and several physiological measurements. We highlight GIPR, a potential diabetes drug target, as possibly implicated in the genetic control of urinary potassium excretion, and NRBP1, a locus associated with gout, as plausibly involved in sodium and albumin excretion. Overall, we identified 22 novel genome-wide significant associations with urinary biomarkers and confirmed several previously established associations, providing new insights into the genetic basis of these traits and their connection to chronic diseases.},
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Urine biomarkers reflecting kidney function and handling of dietary sodium and potassium are strongly associated with several common diseases including chronic kidney disease, cardiovascular disease, and diabetes mellitus. Knowledge about the genetic determinants of these biomarkers may shed light on pathophysiological mechanisms underlying the development of these diseases. We performed genome-wide association studies of urinary albumin: creatinine ratio (UACR), urinary potassium: creatinine ratio (UK/UCr), urinary sodium: creatinine ratio (UNa/UCr) and urinary sodium: potassium ratio (UNa/UK) in up to 218,450 (discovery) and 109,166 (replication) unrelated individuals of European ancestry from the UK Biobank. Further, we explored genetic correlations, tissue-specific gene expression, and possible genes implicated in the regulation of these biomarkers. After replication, we identified 19 genome-wide significant independent loci associated with UACR, 6 each with UK/UCr and UNa/UCr, and 4 with UNa/UK. In addition to 22 novel associations, we confirmed several established associations, including between the CUBN locus and microalbuminuria. We detected high pairwise genetic correlation across the urinary biomarkers, and between their levels and several physiological measurements. We highlight GIPR, a potential diabetes drug target, as possibly implicated in the genetic control of urinary potassium excretion, and NRBP1, a locus associated with gout, as plausibly involved in sodium and albumin excretion. Overall, we identified 22 novel genome-wide significant associations with urinary biomarkers and confirmed several previously established associations, providing new insights into the genetic basis of these traits and their connection to chronic diseases.
2018
Fukaya, E.; Flores, A. M.; Lindholm, D.; Gustafsson, S.; Zanetti, D.; Ingelsson, E.; Leeper, N. J.
Clinical and Genetic Đeterminants of Varicose Veins Journal Article
In: Circulation, 138 (25), pp. 2869–2880, 2018.
@article{pmid30566020,
title = {Clinical and Genetic Đeterminants of Varicose Veins},
author = {E. Fukaya and A. M. Flores and D. Lindholm and S. Gustafsson and D. Zanetti and E. Ingelsson and N. J. Leeper},
year = {2018},
date = {2018-12-01},
journal = {Circulation},
volume = {138},
number = {25},
pages = {2869--2880},
abstract = {Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. ). Using data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.},
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Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. ). Using data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.
Zanetti, D.; Tikkanen, E.; Gustafsson, S.; Priest, J. R.; Burgess, S.; Ingelsson, E.
Birthweight, Ŧype 2 Điabetes Mellitus, and Cardiovascular Đisease: Addressing the Barker Ħypothesis With Mendelian Randomization Journal Article
In: Circ Genom Precis Med, 11 (6), pp. e002054, 2018.
@article{pmid29875125,
title = {Birthweight, Ŧype 2 Điabetes Mellitus, and Cardiovascular Đisease: Addressing the Barker Ħypothesis With Mendelian Randomization},
author = {D. Zanetti and E. Tikkanen and S. Gustafsson and J. R. Priest and S. Burgess and E. Ingelsson},
year = {2018},
date = {2018-06-01},
journal = {Circ Genom Precis Med},
volume = {11},
number = {6},
pages = {e002054},
abstract = {Low birthweight has been associated with a higher risk of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease. The Barker hypothesis posits that intrauterine growth restriction resulting in lower birthweight is causal for these diseases, but causality is difficult to infer from observational studies. 631 individuals from the UK Biobank. Further, we assessed the causal relationship of such associations using Mendelian randomization. , 0.04 and 0.02; per SD change in outcomes and birthweight; 95% CI, 0.03-0.04 and 0.01-0.02, respectively) were positive. The Mendelian randomization analyses indicated inverse causal associations of birthweight with low-density lipoprotein cholesterol, 2-hour glucose, coronary artery disease, and T2D and positive causal association with body mass index but no associations with blood pressure. Our study indicates that lower birthweight, used as a proxy for intrauterine growth retardation, is causally related with increased susceptibility to coronary artery disease and T2D. This causal relationship is not mediated by adult obesity or hypertension.},
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Low birthweight has been associated with a higher risk of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease. The Barker hypothesis posits that intrauterine growth restriction resulting in lower birthweight is causal for these diseases, but causality is difficult to infer from observational studies. 631 individuals from the UK Biobank. Further, we assessed the causal relationship of such associations using Mendelian randomization. , 0.04 and 0.02; per SD change in outcomes and birthweight; 95% CI, 0.03-0.04 and 0.01-0.02, respectively) were positive. The Mendelian randomization analyses indicated inverse causal associations of birthweight with low-density lipoprotein cholesterol, 2-hour glucose, coronary artery disease, and T2D and positive causal association with body mass index but no associations with blood pressure. Our study indicates that lower birthweight, used as a proxy for intrauterine growth retardation, is causally related with increased susceptibility to coronary artery disease and T2D. This causal relationship is not mediated by adult obesity or hypertension.
2016
Zanetti, D.; Via, M.; Carreras-Torres, R.; Esteban, E.; Chaabani, H.; Anaibar, F.; Harich, N.; Habbal, R.; Ghalim, N.; Moral, P.
Analysis of Genomic Regions Associated With Coronary Artery Đisease Reveals Continent-Specific Single Nucleotide Polymorphisms in North African Populations Journal Article
In: J Epidemiol, 26 (5), pp. 264–271, 2016.
@article{pmid26780859,
title = {Analysis of Genomic Regions Associated With Coronary Artery Đisease Reveals Continent-Specific Single Nucleotide Polymorphisms in North African Populations},
author = {D. Zanetti and M. Via and R. Carreras-Torres and E. Esteban and H. Chaabani and F. Anaibar and N. Harich and R. Habbal and N. Ghalim and P. Moral},
year = {2016},
date = {2016-05-01},
journal = {J Epidemiol},
volume = {26},
number = {5},
pages = {264--271},
abstract = {In recent years, several genomic regions have been robustly associated with coronary artery disease (CAD) in different genome-wide association studies (GWASs) conducted mainly in people of European descent. These kinds of data are lacking in African populations, even though heart diseases are a major cause of premature death and disability. Here, 384 single nucleotide polymorphisms (SNPs) in the top four CAD risk regions (1p13, 1q41, 9p21, and 10q11) were genotyped in 274 case-control samples from Morocco and Tunisia, with the aim of analyzing for the first time if the associations found in European populations were transferable to North Africans. The results indicate that, as in Europe, these four genetic regions are also important for CAD risk in North Africa. However, the individual SNPs associated with CAD in Africa are different from those identified in Europe in most cases (1p13, 1q41, and 9p21). Moreover, the seven risk variants identified in North Africans are efficient in discriminating between cases and controls in North African populations, but not in European populations. This study indicates a disparity in markers associated to CAD susceptibility between North Africans and Europeans that may be related to population differences in the chromosomal architecture of these risk regions.},
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In recent years, several genomic regions have been robustly associated with coronary artery disease (CAD) in different genome-wide association studies (GWASs) conducted mainly in people of European descent. These kinds of data are lacking in African populations, even though heart diseases are a major cause of premature death and disability. Here, 384 single nucleotide polymorphisms (SNPs) in the top four CAD risk regions (1p13, 1q41, 9p21, and 10q11) were genotyped in 274 case-control samples from Morocco and Tunisia, with the aim of analyzing for the first time if the associations found in European populations were transferable to North Africans. The results indicate that, as in Europe, these four genetic regions are also important for CAD risk in North Africa. However, the individual SNPs associated with CAD in Africa are different from those identified in Europe in most cases (1p13, 1q41, and 9p21). Moreover, the seven risk variants identified in North Africans are efficient in discriminating between cases and controls in North African populations, but not in European populations. This study indicates a disparity in markers associated to CAD susceptibility between North Africans and Europeans that may be related to population differences in the chromosomal architecture of these risk regions.
2015
Zanetti, D.; Carreras-Torres, R.; Esteban, E.; Via, M.; Moral, P.
Potential Signals of Natural Selection in the Ŧop Risk Loci for Coronary Artery Đisease: 9p21 and 10q11 Journal Article
In: PLoS One, 10 (8), pp. e0134840, 2015.
@article{pmid26252781,
title = {Potential Signals of Natural Selection in the Ŧop Risk Loci for Coronary Artery Đisease: 9p21 and 10q11},
author = {D. Zanetti and R. Carreras-Torres and E. Esteban and M. Via and P. Moral},
year = {2015},
date = {2015-01-01},
journal = {PLoS One},
volume = {10},
number = {8},
pages = {e0134840},
abstract = {Coronary artery disease (CAD) is a complex disease and the leading cause of death in the world. Populations of different ancestry do not always share the same risk markers. Natural selective processes may be the cause of some of the population differences detected for specific risk mutations. In this study, 384 single nucleotide polymorphisms (SNPs) located in four genomic regions associated with CAD (1p13, 1q41, 9p21 and 10q11) are analysed in a set of 19 populations from Europe, Middle East and North Africa and also in Asian and African samples from the 1000 Genomes Project. The aim of this survey is to explore for the first time whether the genetic variability in these genomic regions is better explained by demography or by natural selection. The results indicate significant differences in the structure of genetic variation and in the LD patterns among populations that probably explain the population disparities found in markers of susceptibility to CAD. The results are consistent with potential signature of positive selection in the 9p21 region and of balancing selection in the 9p21 and 10q11. Specifically, in Europe three CAD risk markers in the 9p21 region (rs9632884, rs1537371 and rs1333042) show consistent signals of positive selection. The results of this study are consistent with a potential selective role of CAD in the configuration of genetic diversity in current human populations.},
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Coronary artery disease (CAD) is a complex disease and the leading cause of death in the world. Populations of different ancestry do not always share the same risk markers. Natural selective processes may be the cause of some of the population differences detected for specific risk mutations. In this study, 384 single nucleotide polymorphisms (SNPs) located in four genomic regions associated with CAD (1p13, 1q41, 9p21 and 10q11) are analysed in a set of 19 populations from Europe, Middle East and North Africa and also in Asian and African samples from the 1000 Genomes Project. The aim of this survey is to explore for the first time whether the genetic variability in these genomic regions is better explained by demography or by natural selection. The results indicate significant differences in the structure of genetic variation and in the LD patterns among populations that probably explain the population disparities found in markers of susceptibility to CAD. The results are consistent with potential signature of positive selection in the 9p21 region and of balancing selection in the 9p21 and 10q11. Specifically, in Europe three CAD risk markers in the 9p21 region (rs9632884, rs1537371 and rs1333042) show consistent signals of positive selection. The results of this study are consistent with a potential selective role of CAD in the configuration of genetic diversity in current human populations.
- Monserrato
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