Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

Joshua C. Randall; Thomas W. Winkler; Zoltan Kutalik; Sonja I. Berndt; Anne U. Jackson; Keri L. Monda; Tuomas O. Kilpelaeinen; Tonu Esko; Reedik Maegi; Shengxu Li; Tsegaselassie Workalemahu; Mary F. Feitosa; Damien C. Croteau-Chonka; Felix R. Day; Tove Fall; Teresa Ferreira; Stefan Gustafsson; Adam E. Locke; Iain Mathieson; Andre Scherag; Sailaja Vedantam; Andrew R. Wood; Liming Liang; Valgerdur Steinthorsdottir; Gudmar Thorleifsson; Emmanouil T. Dermitzakis; Antigone S. Dimas; Fredrik Karpe; Josine L. Min; George Nicholson; Deborah J. Clegg; Thomas Person; Jon P. Krohn; Sabrina Bauer; Christa Buechler; Kristina Eisinger; Amelie Bonnefond; Philippe Froguel; Jouke-Jan Hottenga; Inga Prokopenko; Lindsay L. Waite; Tamara B. Harris; Albert Vernon Smith; Alan R. Shuldiner; Wendy L. McArdle; Mark J. Caulfield; Patricia B. Munroe; Henrik Gronberg; Yii-Der Ida Chen; Guo Li; Jacques S. Beckmann; Toby Johnson; Unnur Thorsteinsdottir; Maris Teder-Laving; Kay-Tee Khaw; Nicholas J. Wareham; Jing Hua Zhao; Najaf Amin; Ben A. Oostra; Aldi T. Kraja; Michael A. Province; L. Adrienne Cupples; Nancy L. Heard-Costa; Jaakko Kaprio; Samuli Ripatti; Ida Surakka; Francis S. Collins; Jouko Saramies; Jaakko Tuomilehto; Antti Jula; Veikko Salomaa; Jeanette Erdmann; Christian Hengstenberg; Christina Loley; Heribert Schunkert; Claudia Lamina; H. Erich Wichmann; Eva Albrecht; Christian Gieger; Andrew A. Hicks; Asa Johansson; Peter P. Pramstaller; Sekar Kathiresan; Elizabeth K. Speliotes; Brenda Penninx; Anna-Liisa Hartikainen; Marjo-Riitta Jarvelin; Ulf Gyllensten; Dorret I. Boomsma; Harry Campbell; James F. Wilson; Stephen J. Chanock; Martin Farrall; Anuj Goel; Carolina Medina-Gomez; Fernando Rivadeneira; Karol Estrada; Andre G. Uitterlinden; Albert Hofman; M. Carola Zillikens; DIAGRAM Consortium

doi:10.1371/journal.pgen.1003500

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Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

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Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

Joshua C. Randall, Thomas W. Winkler, Zoltan Kutalik, Sonja I. Berndt, Anne U. Jackson, Keri L. Monda, Tuomas O. Kilpelaeinen, Tonu Esko, Reedik Maegi, Shengxu Li, …

PLoS genetics, Vol.9(6), pp.e1003500-e1003500

01/06/2013

DOI: https://doi.org/10.1371/journal.pgen.1003500

PMID: 23754948

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5x10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

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Title: Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits
Creators: Joshua C. Randall - Wellcome Centre for Human Genetics
Thomas W. Winkler - University of Regensburg
Zoltan Kutalik - University of Lausanne
Sonja I. Berndt - National Cancer Institute
Anne U. Jackson - University of Michigan–Ann Arbor
Keri L. Monda - University of North Carolina at Chapel Hill
Tuomas O. Kilpelaeinen - Massachusetts Rehabilitation Commission
Tonu Esko - University of Tartu
Reedik Maegi - University of Oxford
Shengxu Li - MRC Epidemiology Unit
Tsegaselassie Workalemahu - Harvard University
Mary F. Feitosa - Washington University in St. Louis
Damien C. Croteau-Chonka - Univ N Carolina, Dept Genet, Chapel Hill, NC USA
Felix R. Day - MRC Epidemiology Unit
Tove Fall - Karolinska Institutet
Teresa Ferreira - Wellcome Centre for Human Genetics
Stefan Gustafsson - Karolinska Institutet
Adam E. Locke - Michigan United
Iain Mathieson - Wellcome Centre for Human Genetics
Andre Scherag - Institut für Medizinische Informatik, Biometrie und Epidemiologie
Sailaja Vedantam - Boston Children's Hospital
Andrew R. Wood - University of Exeter
Liming Liang - Harvard University
Valgerdur Steinthorsdottir - deCODE Genet, Reykjavik, Iceland
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Emmanouil T. Dermitzakis - University of Geneva
Antigone S. Dimas - Alexander Fleming Biomedical Sciences Research Center
Fredrik Karpe - Oxford Centre for Diabetes, Endocrinology and Metabolism
Josine L. Min - Wellcome Centre for Human Genetics
George Nicholson - University of Oxford
Deborah J. Clegg - The University of Texas Southwestern Medical Center
Thomas Person - The University of Texas Southwestern Medical Center
Jon P. Krohn - Wellcome Centre for Human Genetics
Sabrina Bauer - University Hospital Regensburg
Christa Buechler - University Hospital Regensburg
Kristina Eisinger - University Hospital Regensburg
Amelie Bonnefond - Institut Pasteur de Lille
Philippe Froguel - Imperial College London
Jouke-Jan Hottenga - University of Amsterdam
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Lindsay L. Waite - HudsonAlpha Institute for Biotechnology
Tamara B. Harris - National Institute on Aging
Albert Vernon Smith - University of Iceland
Alan R. Shuldiner - University of Maryland, Baltimore
Wendy L. McArdle - University of Bristol
Mark J. Caulfield - William Harvey Research Institute
Patricia B. Munroe - Queen Mary University of London
Henrik Gronberg - Karolinska Institutet
Yii-Der Ida Chen - Cedars-Sinai Medical Center
Guo Li - University of Washington
Jacques S. Beckmann - University of Lausanne
Toby Johnson - University of Lausanne
Unnur Thorsteinsdottir - deCODE Genet, Reykjavik, Iceland
Maris Teder-Laving - University of Tartu
Kay-Tee Khaw - University of Cambridge
Nicholas J. Wareham - MRC Epidemiology Unit
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Najaf Amin - Erasmus University Rotterdam
Ben A. Oostra - Erasmus MC
Aldi T. Kraja - Washington University in St. Louis
Michael A. Province - Washington University in St. Louis
L. Adrienne Cupples - Boston University
Nancy L. Heard-Costa - Boston University
Jaakko Kaprio - Finnish Institute for Health and Welfare
Samuli Ripatti - Institute for Molecular Medicine Finland
Ida Surakka - Institute for Molecular Medicine Finland
Francis S. Collins - National Human Genome Research Institute
Jouko Saramies - South Karelia Central Hospital
Jaakko Tuomilehto - Finnish Institute for Health and Welfare
Antti Jula - Finnish Institute for Health and Welfare
Veikko Salomaa - Finnish Institute for Health and Welfare
Jeanette Erdmann - University of Lübeck
Christian Hengstenberg - University of Lübeck
Christina Loley - German Centre for Cardiovascular Research
Heribert Schunkert - Deutsches Herzzentrum München
Claudia Lamina - Innsbruck Medical University
H. Erich Wichmann - Helmholtz Zentrum München
Eva Albrecht - Helmholtz Zentrum München
Christian Gieger - Helmholtz Zentrum München
Andrew A. Hicks - Eurac Research
Asa Johansson - Uppsala University
Peter P. Pramstaller - Eurac Research
Sekar Kathiresan - Massachusetts General Hospital
Elizabeth K. Speliotes - University of Michigan–Ann Arbor
Brenda Penninx - University of Groningen
Anna-Liisa Hartikainen - University of Oulu
Marjo-Riitta Jarvelin - University of London
Ulf Gyllensten - Uppsala University
Dorret I. Boomsma - Vrije Universiteit Amsterdam
Harry Campbell - University of Edinburgh
James F. Wilson - University of Edinburgh
Stephen J. Chanock - National Institutes of Health
Martin Farrall - University of Oxford
Anuj Goel - University of Oxford
Carolina Medina-Gomez - Erasmus MC
Fernando Rivadeneira - Erasmus MC
Karol Estrada - Erasmus MC
Andre G. Uitterlinden - Netherlands Consortium for Healthy Ageing
Albert Hofman - Erasmus MC
M. Carola Zillikens - Erasmus MC
DIAGRAM Consortium
Publication Details: PLoS genetics, Vol.9(6), pp.e1003500-e1003500
Publisher: Public Library Science
Number of pages: 19
Date published: 01/06/2013
Grant note: Dresden University of Technology Funding Grant Heinz Nixdorf Foundation National Alliance for Research on Schizophrenia and Depression (NARSAD); Agence Nationale de la Recherche (ANR); NARSAD German Diabetes Association Netherlands Centre for Medical Systems Biology (CMSB) British Heart Foundation Academy of Finland Centre of Excellence in Complex Disease Genetics; Research Council of Finland Vastra Gotaland Foundation Genetic Association Information Network (GAIN) London Cardiovascular Biomedical Research Unit
Identifiers: 99928710002346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

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