Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Iris M. Heid; Anne U. Jackson; Joshua C. Randall; Thomas W. Winkler; Lu Qi; Valgerdur Steinthorsdottir; Gudmar Thorleifsson; M. Carola Zillikens; Elizabeth K. Speliotes; Reedik Maegi; Tsegaselassie Workalemahu; Charles C. White; Nabila Bouatia-Naji; Tamara B. Harris; Sonja I. Berndt; Erik Ingelsson; Cristen J. Willer; Michael N. Weedon; Jianan Luan; Sailaja Vedantam; Tonu Esko; Tuomas O. Kilpelaeinen; Zoltan Kutalik; Shengxu Li; Keri L. Monda; Anna L. Dixon; Christopher C. Holmes; Lee M. Kaplan; Liming Liang; Josine L. Min; Miriam F. Moffatt; Cliona Molony; George Nicholson; Eric E. Schadt; Krina T. Zondervan; Mary F. Feitosa; Teresa Ferreira; Hana Lango Allen; Robert J. Weyant; Eleanor Wheeler; Andrew R. Wood; Karol Estrada; Michael E. Goddard; Guillaume Lettre; Massimo Mangino; Dale R. Nyholt; Shaun Purcell; Albert Vernon Smith; Peter M. Visscher; Jian Yang; Steven A. McCarroll; James Nemesh; Benjamin F. Voight; Devin Absher; Najaf Amin; Thor Aspelund; Lachlan Coin; Nicole L. Glazer; Caroline Hayward; Nancy L. Heard-Costa; Jouke-Jan Hottenga; Asa Johansson; Toby Johnson; Marika Kaakinen; Karen Kapur; Shamika Ketkar; Joshua W. Knowles; Peter Kraft; Aldi T. Kraja; Claudia Lamina; Michael F. Leitzmann; Barbara McKnight; Andrew P. Morris; Ken K. Ong; John R. B. Perry; Marjolein J. Peters; Ozren Polasek; Inga Prokopenko; Nigel W. Rayner; Samuli Ripatti; Fernando Rivadeneira; Neil R. Robertson; Serena Sanna; Ulla Sovio; Ida Surakka; Alexander Teumer; Sophie van Wingerden; Veronique Vitart; Jing Hua Zhao; Christine Cavalcanti-Proenca; Peter S. Chines; Eva Fisher; Jennifer R. Kulzer; Cecile Lecoeur; Narisu Narisu; Camilla Sandholt; Laura J. Scott; Kaisa Silander; Klaus Stark; Mari-Liis Tammesoo; MAGIC

doi:10.1038/ng.685

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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Iris M. Heid, Anne U. Jackson, Joshua C. Randall, Thomas W. Winkler, Lu Qi, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, M. Carola Zillikens, Elizabeth K. Speliotes, Reedik Maegi, …

Nature genetics, Vol.42(11), pp.949-U160

01/11/2010

DOI: https://doi.org/10.1038/ng.685

PMID: 20935629

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

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Title: Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
Creators: Iris M. Heid - College Station Medical Center
Anne U. Jackson - University of Michigan–Ann Arbor
Joshua C. Randall - Wellcome Centre for Human Genetics
Thomas W. Winkler - College Station Medical Center
Lu Qi - Harvard University
Valgerdur Steinthorsdottir - deCODE Genet, Reykjavik, Iceland
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
M. Carola Zillikens - Erasmus MC
Elizabeth K. Speliotes - Broad Institute
Reedik Maegi - University of Oxford
Tsegaselassie Workalemahu - Harvard University
Charles C. White - Boston University
Nabila Bouatia-Naji - Inst Pasteur, IBL, UMR8199, CNRS, F-59019 Lille, France
Tamara B. Harris - National Institute on Aging
Sonja I. Berndt - National Cancer Institute
Erik Ingelsson - Karolinska Institutet
Cristen J. Willer - University of Michigan–Ann Arbor
Michael N. Weedon - University of Exeter
Jianan Luan - Massachusetts Rehabilitation Commission
Sailaja Vedantam - Broad Institute
Tonu Esko - University of Tartu
Tuomas O. Kilpelaeinen - Massachusetts Rehabilitation Commission
Zoltan Kutalik - University of Lausanne
Shengxu Li - MRC Epidemiology Unit
Keri L. Monda - University of North Carolina at Chapel Hill
Anna L. Dixon - University of Bath
Christopher C. Holmes - Massachusetts Rehabilitation Commission
Lee M. Kaplan - Massachusetts General Hospital
Liming Liang - Harvard University
Josine L. Min - Leiden University Medical Center
Miriam F. Moffatt - Imperial College London
Cliona Molony - MSD
George Nicholson - University of Oxford
Eric E. Schadt - Pacific Biosciences
Krina T. Zondervan - Wellcome Centre for Human Genetics
Mary F. Feitosa - Washington University in St. Louis
Teresa Ferreira - Wellcome Centre for Human Genetics
Hana Lango Allen - University of Exeter
Robert J. Weyant - University of Michigan–Ann Arbor
Eleanor Wheeler - Wellcome Sanger Institute
Andrew R. Wood - University of Exeter
Karol Estrada - Erasmus MC
Michael E. Goddard - University of Melbourne
Guillaume Lettre - Montreal Heart Institute
Massimo Mangino - King's College London
Dale R. Nyholt - QIMR Berghofer Medical Research Institute
Shaun Purcell - Center for Human Genetics
Albert Vernon Smith - Icelandic Heart Association
Peter M. Visscher - QIMR Berghofer Medical Research Institute
Jian Yang - QIMR Berghofer Medical Research Institute
Steven A. McCarroll - Center for Human Genetics
James Nemesh - Broad Institute
Benjamin F. Voight - Center for Human Genetics
Devin Absher - HudsonAlpha Institute for Biotechnology
Najaf Amin - Erasmus University Rotterdam
Thor Aspelund - Icelandic Heart Association
Lachlan Coin - Imperial College London
Nicole L. Glazer - University of Washington
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Nancy L. Heard-Costa - Boston University
Jouke-Jan Hottenga - University of Amsterdam
Asa Johansson - Uppsala University
Toby Johnson - University of Lausanne
Marika Kaakinen - University of Oulu
Karen Kapur - University of Lausanne
Shamika Ketkar - Washington University in St. Louis
Joshua W. Knowles - Stanford University
Peter Kraft - Harvard University
Aldi T. Kraja - Washington University in St. Louis
Claudia Lamina - Helmholtz Zentrum München
Michael F. Leitzmann - College Station Medical Center
Barbara McKnight - University of Washington
Andrew P. Morris - Wellcome Centre for Human Genetics
Ken K. Ong - MRC Epidemiology Unit
John R. B. Perry - Peninsula College of Medicine and Dentistry
Marjolein J. Peters - Netherlands Consortium for Healthy Ageing
Ozren Polasek - Andrija Stampar Teaching Institute of Public Health
Inga Prokopenko - Wellcome Centre for Human Genetics
Nigel W. Rayner - University of Oxford
Samuli Ripatti - Institute for Molecular Medicine Finland
Fernando Rivadeneira - Netherlands Consortium for Healthy Ageing
Neil R. Robertson - University of Oxford
Serena Sanna - Institute of Genetic and Biomedical Research
Ulla Sovio - Imperial College London
Ida Surakka - University of Helsinki
Alexander Teumer - Universität Greifswald
Sophie van Wingerden - Erasmus MC
Veronique Vitart - MRC Institute of Genetics and Molecular Medicine
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Christine Cavalcanti-Proenca - Université Lille Nord de France
Peter S. Chines - National Human Genome Research Institute
Eva Fisher - German Institute of Human Nutrition
Jennifer R. Kulzer - University of North Carolina at Chapel Hill
Cecile Lecoeur - Inst Pasteur, IBL, UMR8199, CNRS, F-59019 Lille, France
Narisu Narisu - National Human Genome Research Institute
Camilla Sandholt - Hagedorn Res Inst, Gentofte, Denmark
Laura J. Scott - University of Michigan–Ann Arbor
Kaisa Silander - Institute for Molecular Medicine Finland
Klaus Stark - University Hospital Regensburg
Mari-Liis Tammesoo - University of Tartu
MAGIC
Publication Details: Nature genetics, Vol.42(11), pp.949-U160
Publisher: Springer Nature
Number of pages: 14
Date published: 01/11/2010
Grant note: Torsten and Ragnar Soderberg's Foundation Social Ministry of the Federal State of Mecklenburg-West Pomerania, Germany Danish Pharmaceutical Association Finska Lakaresallskapet 014-93-015 / Research Institute for Diseases in the Elderly Support for Science Funding programme Vastra Gotaland Foundation ALF/LUA Gothenburg 33CSCO-122661 / Swiss National Science Foundation; Swiss National Science Foundation (SNSF) Healthway, Western Australia
Identifiers: 99928740302346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

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