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 Mägi;
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Tsegaselassie Workalemahu;
Charles C White;
Nabila Bouatia-Naji;
Tamara B Harris;
Sonja I Berndt;
Erik Ingelsson;
Cristen J Willer;
Michael N Weedon;
Jian'an Luan;
Sailaja Vedantam;
Tõnu Esko;
Tuomas O Kilpeläinen;
Zoltán 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;
MAGIC;
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Guillaume Lettre;
Massimo Mangino;
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Shaun Purcell;
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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;
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Marika Kaakinen;
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Shamika Ketkar;
Joshua W Knowles;
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Aldi T Kraja;
Claudia Lamina;
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Barbara McKnight;
Andrew P Morris;
Ken K Ong;
John RB 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-Proença;
Peter S Chines;
Eva Fisher;
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Cecile Lecoeur;
Narisu Narisu;
Camilla Sandholt;
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Nicholas John Timpson;
Richard M Watanabe;
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Johannes Kettunen;
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Niina Pellikka;
Markus Perola;
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Helene Alavere;
Peter Almgren;
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Amanda J Bennett;
Reiner Biffar;
Lori L Bonnycastle;
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Torben Jørgensen;
Fredrik Karpe;
Kay-Tee Khaw;
Markku Laakso;
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Michel Marre;
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Gudny Eiriksdottir;
Vilmundur Gudnason;
Ulf Gyllensten;
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Carlos Iribarren;
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WH Linda Kao;
Jaakko Kaprio;
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Ben Oostra;
Brenda W Penninx;
Peter P Pramstaller;
Bruce M Psaty;
Thomas Quertermous;
Aila Rissanen;
Igor Rudan;
Alan R Shuldiner;
Nicole Soranzo;
Timothy D Spector;
Ann-Christine Syvanen;
Manuela Uda;
André Uitterlinden;
Henry Völzke;
Peter Vollenweider;
James F Wilson;
Jacqueline C Witteman;
Alan F Wright;
Gonçalo R Abecasis;
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Panos Deloukas;
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Leif C Groop;
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Unnur Thorsteinsdottir;
Cornelia M van Duijn;
Kari Stefansson;
L Adrienne Cupples;
Ruth JF Loos;
Inês Barroso;
Mark I McCarthy;
Caroline S Fox;
Karen L Mohlke;
Cecilia M Lindgren;
(2010)
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
Nature genetics, 42 (11).
pp. 949-960.
ISSN 1061-4036
DOI: 10.1038/ng.685
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 × 10⁻⁹ to P = 1.8 × 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 × 10⁻³ to P = 1.2 × 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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- Available under Creative Commons: NC-ND 3.0
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