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

Iris M. Heid | Zendy; Anne Jackson | Zendy; Joshua C. Randall | Zendy; Thomas W. Winkler | Zendy; Lu Qi | Zendy; Valgerður Steinthórsdóttir | Zendy; Guðmar Þorleifsson | Zendy; M. Carola Zillikens | Zendy; Elizabeth K. Speliotes | Zendy; Reedik Mägi | Zendy; Tsegaselassie Workalemahu | Zendy; Charles C. White | Zendy; Nabila BouatiaNaji | Zendy; Tamara B. Harris | Zendy; Sonja I. Berndt | Zendy; Erik Ingelsson | Zendy; Cristen J. Willer | Zendy; Michael N. Weedon | Zendy; Jian’an Luan | Zendy; Sailaja Vedantam | Zendy; Tõnu Esko | Zendy; Tuomas O. Kilpeläinen | Zendy; Zoltán Kutalik | Zendy; Shengxu Li | Zendy; Keri L. Monda | Zendy; Anna Dixon | Zendy; Chris Holmes | Zendy; Lee M. Kaplan | Zendy; Liming Liang | Zendy; Josine L. Min | Zendy; Miriam F. Moffatt | Zendy; Cliona Molony | Zendy; Geoffrey C. Nicholson | Zendy; Eric E. Schadt | Zendy; Krina T. Zondervan | Zendy; Mary F. Feitosa | Zendy; Teresa Ferreira | Zendy; Hana Lango Allen | Zendy; Robert J. 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Open Access

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

Author(s) -

Iris M. Heid,

Anne Jackson,

Joshua C. Randall,

Thomas W. Winkler,

Lu Qi,

Valgerður Steinthórsdóttir,

Guðmar Þorleifsson,

M. Carola Zillikens,

Elizabeth K. Speliotes,

Reedik Mägi,

Tsegaselassie Workalemahu,

Charles C. White,

Nabila BouatiaNaji,

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 Dixon,

Chris Holmes,

Lee M. Kaplan,

Liming Liang,

Josine L. Min,

Miriam F. Moffatt,

Cliona Molony,

Geoffrey C. 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 V. 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. HeardCosta,

JoukeJan Hottenga,

Åsa 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 Polašek,

Inga Prokopenko,

Nigel W. Rayner,

Samuli Ripatti,

Fernando Rivadeneira,

Neil R. Robertson,

Serena Sanna,

Ulla Sovio,

Ida Surakka,

Alexander Teumer,

S. van Wingerden,

Véronique Vitart,

Wei Zhao,

Christine Cavalcanti-Proença,

Peter S. Chines,

Eva Fisher,

Jennifer R. Kulzer,

Cécile Lecœur,

Narisu Narisu,

Camilla H. Sandholt,

Laura J. Scott,

Kaisa Silander,

Klaus Stark,

MariLiis Tammesoo,

Tanya M. Teslovich,

Nicholas J. Timpson,

Richard M. Watanabe,

Ryan Welch,

Daniel I. Chasman,

Matthew N. Cooper,

JohnOlov Jansson,

Johannes Kettunen,

Robert Lawrence,

Niina Pellikka,

Markus Perola,

Liesbeth Vandenput,

Helene Alavere,

Peter Almgren,

Larry D. Atwood,

Amanda J. Bennett,

Reiner Biffar,

Lori L. Bonnycastle,

Stefan R. Bornstein,

Thomas A. Buchanan,

Harry Campbell,

Ian N.M. Day,

Mariano Dei,

Marcus Dörr,

Paul Elliott,

Michael R. Erdos,

Johan G. Eriksson,

Nelson B. Freimer,

Mao Fu,

Stefan Gaget,

Eco J. C. de Geus,

Anette P. Gjesing,

Harald Grallert,

Jürgen Gräßler,

Christopher J. Groves,

Candace Guiducci,

AnnaLiisa Hartikainen,

Neelam Hassanali,

Aki S. Havulinna,

KarlHeinz Herzig,

Andrew A. Hicks,

Jennie Hui,

Wilmar Igl,

Jari Lahti,

Antti Jula,

Eero Kajantie,

Leena Kinnunen,

Ivana Kolčić,

Seppo Koskinen,

Péter Kovács,

Heyo K. Kroemer,

Vjekoslav Krželj,

Johanna Kuusisto,

Kirsti Kvaløy,

Jaana Laitinen,

Olivier Lantieri,

G.M. Lathrop,

MarjaLiisa Lokki,

Robert Luben,

Barbara Ludwig,

Wendy L. McArdle,

Anne McCarthy,

Mario A. Morken,

Mari Nelis,

Matt J. Neville,

Guillaume Paré,

Alex Parker,

John F. Peden,

Irene Pichler,

Kirsi H. Pietiläinen,

Carl Platou,

Anneli Pouta,

Martin Ridderstråle,

Nilesh J. Samani,

Jouko Saramies,

Juha Sinisalo,

Jan Smit,

Rona J. Strawbridge,

Heather M. Stringham,

Amy J. Swift,

Maris TederLaving,

Brian Thomson,

Gianluca Usala,

Joyce B. J. van Meurs,

GertJan B. van Ommen,

Vincent Vatin,

Cláudia B. Volpato,

Henri Wallaschofski,

G. Bragi Walters,

Elisabeth Widén,

Sarah H. Wild,

Gonneke Willemsen,

Daniel R. Witte,

Lina Zgaga,

Paavo Zitting,

John Beilby,

Anthony James,

Mika Kähönen,

Terho Lehtimäki,

Markku S. Nieminen,

Claes Ohlsson,

Lyle J. Palmer,

Olli Raitakari,

Paul M. Ridker,

Michael Stümvoll,

Anke Tönjes,

Jorma Viikari,

Beverley Balkau,

Yoav BenShlomo,

Richard N. Bergman,

Heiner Boeing,

George Davey Smith,

Shah Ebrahim,

Philippe Froguel,

Torben Hansen,

Christian Hengstenberg,

Kristian Hveem,

Bo Isomaa,

Torben Jørgensen,

Fredrik Karpe,

KayTee Khaw,

Markku Laakso,

Debbie A. Lawlor,

Michel Marre,

Thomas Meitinger,

Andres Metspalu,

Kristian Midthjell,

Oluf Pedersen,

Veikko Salomaa,

Peter Schwarz,

Jaakko Tuomilehto,

Timo T. Valle,

Nicholas J. Wareham,

Alice M. Arnold,

J. Beckmann,

Sven Bergmann,

Eric Boerwinkle,

Dorret I. Boomsma,

Mark J. Caulfield,

Francis S. Collins,

Guðný Eiríksdóttir,

Vilmundur Guðnason,

Ulf Gyllensten,

Anders Hamsten,

Andrew T. Hattersley,

Albert Hofman,

Frank B. Hu,

Thomas Illig,

Carlos Iribarren,

MarjoRiitta Järvelin,

W.H. Linda Kao,

Jaakko Kaprio,

Lenore J. Launer,

Patricia B. Munroe,

Ben A. Oostra,

Brenda W.J.H. Penninx,

Peter P. Pramstaller,

Bruce M. Psaty,

Thomas Quertermous,

Aila Rissanen,

Igor Rudan,

Alan R. Shuldiner,

Nicole Soranzo,

Timothy D. Spector,

AnnChristine Syvänen,

Manuela Uda,

André G. Uitterlinden,

Henry Völzke,

Péter Vollenweider,

James F. Wilson,

Jacqueline C.M. Witteman,

Alan F. Wright,

Gonçalo R. Abecasis,

Michael Boehnke,

Ingrid B. Borecki,

Panos Deloukas,

Timothy M. Frayling,

Leif Groop,

Talin Haritunians,

David J. Hunter,

Robert C. Kaplan,

Kari E. North,

Jeffrey R. O’Connell,

Leena Peltonen,

David Schlessinger,

David P. Strachan,

Joel N. Hirschhorn,

Themistocles L. Assimes,

HErich Wichmann,

Unnur Þorsteinsdóttir,

Cornelia M. van Duijn,

Kári Stéfansson,

L. Adrienne Cupples,

Ruth J. F. Loos,

Inês Barroso,

Mark I. McCarthy,

Caroline S. Fox,

Karen L. Mohlke,

Cecilia M. Lindgren

Publication year - 2010

Publication title -

nature genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 18.861

H-Index - 573

eISSN - 1546-1718

pISSN - 1061-4036

DOI - 10.1038/ng.685

Subject(s) - biology , sexual dimorphism , waist–hip ratio , trait , body fat percentage , body mass index , genetics , quantitative trait locus , genome wide association study , anthropometry , meta analysis , waist , medicine , gene , single nucleotide polymorphism , genotype , endocrinology , computer science , programming language

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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