Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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20935629
TITLE
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
ABSTRACT
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.
DATE PUBLISHED
2010 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/05/06
accepted 2010/09/15
aheadofprint 2010/10/10
entrez 2010/10/12 06:00
pubmed 2010/10/12 06:00
medline 2010/11/17 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Heid IM Heid Iris M IM Regensburg University Medical Center, Department of Epidemiology and Preventive Medicine, Regensburg, Germany.
Jackson AU Jackson Anne U AU
Randall JC Randall Joshua C JC
Winkler TW Winkler Thomas W TW
Qi L Qi Lu L
Steinthorsdottir V Steinthorsdottir Valgerdur V
Thorleifsson G Thorleifsson Gudmar G
Zillikens MC Zillikens M Carola MC
Speliotes EK Speliotes Elizabeth K EK
Mägi R Mägi Reedik R
Workalemahu T Workalemahu Tsegaselassie T
White CC White Charles C CC
Bouatia-Naji N Bouatia-Naji Nabila N
Harris TB Harris Tamara B TB
Berndt SI Berndt Sonja I SI
Ingelsson E Ingelsson Erik E
Willer CJ Willer Cristen J CJ
Weedon MN Weedon Michael N MN
Luan J Luan Jian'an J
Vedantam S Vedantam Sailaja S
Esko T Esko Tõnu T
Kilpeläinen TO Kilpeläinen Tuomas O TO
Kutalik Z Kutalik Zoltán Z
Li S Li Shengxu S
Monda KL Monda Keri L KL
Dixon AL Dixon Anna L AL
Holmes CC Holmes Christopher C CC
Kaplan LM Kaplan Lee M LM
Liang L Liang Liming L
Min JL Min Josine L JL
Moffatt MF Moffatt Miriam F MF
Molony C Molony Cliona C
Nicholson G Nicholson George G
Schadt EE Schadt Eric E EE
Zondervan KT Zondervan Krina T KT
Feitosa MF Feitosa Mary F MF
Ferreira T Ferreira Teresa T
Lango Allen H Lango Allen Hana H
Weyant RJ Weyant Robert J RJ
Wheeler E Wheeler Eleanor E
Wood AR Wood Andrew R AR
MAGIC
Estrada K Estrada Karol K
Goddard ME Goddard Michael E ME
Lettre G Lettre Guillaume G
Mangino M Mangino Massimo M
Nyholt DR Nyholt Dale R DR
Purcell S Purcell Shaun S
Smith AV Smith Albert Vernon AV
Visscher PM Visscher Peter M PM
Yang J Yang Jian J
McCarroll SA McCarroll Steven A SA
Nemesh J Nemesh James J
Voight BF Voight Benjamin F BF
Absher D Absher Devin D
Amin N Amin Najaf N
Aspelund T Aspelund Thor T
Coin L Coin Lachlan L
Glazer NL Glazer Nicole L NL
Hayward C Hayward Caroline C
Heard-Costa NL Heard-Costa Nancy L NL
Hottenga JJ Hottenga Jouke-Jan JJ
Johansson A Johansson Asa A
Johnson T Johnson Toby T
Kaakinen M Kaakinen Marika M
Kapur K Kapur Karen K
Ketkar S Ketkar Shamika S
Knowles JW Knowles Joshua W JW
Kraft P Kraft Peter P
Kraja AT Kraja Aldi T AT
Lamina C Lamina Claudia C
Leitzmann MF Leitzmann Michael F MF
McKnight B McKnight Barbara B
Morris AP Morris Andrew P AP
Ong KK Ong Ken K KK
Perry JR Perry John R B JR
Peters MJ Peters Marjolein J MJ
Polasek O Polasek Ozren O
Prokopenko I Prokopenko Inga I
Rayner NW Rayner Nigel W NW
Ripatti S Ripatti Samuli S
Rivadeneira F Rivadeneira Fernando F
Robertson NR Robertson Neil R NR
Sanna S Sanna Serena S
Sovio U Sovio Ulla U
Surakka I Surakka Ida I
Teumer A Teumer Alexander A
van Wingerden S van Wingerden Sophie S
Vitart V Vitart Veronique V
Zhao JH Zhao Jing Hua JH
Cavalcanti-Proença C Cavalcanti-Proença Christine C
Chines PS Chines Peter S PS
Fisher E Fisher Eva E
Kulzer JR Kulzer Jennifer R JR
Lecoeur C Lecoeur Cecile C
Narisu N Narisu Narisu N
Sandholt C Sandholt Camilla C
Scott LJ Scott Laura J LJ
Silander K Silander Kaisa K
Stark K Stark Klaus K
Tammesoo ML Tammesoo Mari-Liis ML
Teslovich TM Teslovich Tanya M TM
Timpson NJ Timpson Nicholas John NJ
Watanabe RM Watanabe Richard M RM
Welch R Welch Ryan R
Chasman DI Chasman Daniel I DI
Cooper MN Cooper Matthew N MN
Jansson JO Jansson John-Olov JO
Kettunen J Kettunen Johannes J
Lawrence RW Lawrence Robert W RW
Pellikka N Pellikka Niina N
Perola M Perola Markus M
Vandenput L Vandenput Liesbeth L
Alavere H Alavere Helene H
Almgren P Almgren Peter P
Atwood LD Atwood Larry D LD
Bennett AJ Bennett Amanda J AJ
Biffar R Biffar Reiner R
Bonnycastle LL Bonnycastle Lori L LL
Bornstein SR Bornstein Stefan R SR
Buchanan TA Buchanan Thomas A TA
Campbell H Campbell Harry H
Day IN Day Ian N M IN
Dei M Dei Mariano M
Dörr M Dörr Marcus M
Elliott P Elliott Paul P
Erdos MR Erdos Michael R MR
Eriksson JG Eriksson Johan G JG
Freimer NB Freimer Nelson B NB
Fu M Fu Mao M
Gaget S Gaget Stefan S
Geus EJ Geus Eco J C EJ
Gjesing AP Gjesing Anette P AP
Grallert H Grallert Harald H
Grässler J Grässler Jürgen J
Groves CJ Groves Christopher J CJ
Guiducci C Guiducci Candace C
Hartikainen AL Hartikainen Anna-Liisa AL
Hassanali N Hassanali Neelam N
Havulinna AS Havulinna Aki S AS
Herzig KH Herzig Karl-Heinz KH
Hicks AA Hicks Andrew A AA
Hui J Hui Jennie J
Igl W Igl Wilmar W
Jousilahti P Jousilahti Pekka P
Jula A Jula Antti A
Kajantie E Kajantie Eero E
Kinnunen L Kinnunen Leena L
Kolcic I Kolcic Ivana I
Koskinen S Koskinen Seppo S
Kovacs P Kovacs Peter P
Kroemer HK Kroemer Heyo K HK
Krzelj V Krzelj Vjekoslav V
Kuusisto J Kuusisto Johanna J
Kvaloy K Kvaloy Kirsti K
Laitinen J Laitinen Jaana J
Lantieri O Lantieri Olivier O
Lathrop GM Lathrop G Mark GM
Lokki ML Lokki Marja-Liisa ML
Luben RN Luben Robert N RN
Ludwig B Ludwig Barbara B
McArdle WL McArdle Wendy L WL
McCarthy A McCarthy Anne A
Morken MA Morken Mario A MA
Nelis M Nelis Mari M
Neville MJ Neville Matt J MJ
Paré G Paré Guillaume G
Parker AN Parker Alex N AN
Peden JF Peden John F JF
Pichler I Pichler Irene I
Pietiläinen KH Pietiläinen Kirsi H KH
Platou CG Platou Carl G P CG
Pouta A Pouta Anneli A
Ridderstråle M Ridderstråle Martin M
Samani NJ Samani Nilesh J NJ
Saramies J Saramies Jouko J
Sinisalo J Sinisalo Juha J
Smit JH Smit Jan H JH
Strawbridge RJ Strawbridge Rona J RJ
Stringham HM Stringham Heather M HM
Swift AJ Swift Amy J AJ
Teder-Laving M Teder-Laving Maris M
Thomson B Thomson Brian B
Usala G Usala Gianluca G
van Meurs JB van Meurs Joyce B J JB
van Ommen GJ van Ommen Gert-Jan GJ
Vatin V Vatin Vincent V
Volpato CB Volpato Claudia B CB
Wallaschofski H Wallaschofski Henri H
Walters GB Walters G Bragi GB
Widen E Widen Elisabeth E
Wild SH Wild Sarah H SH
Willemsen G Willemsen Gonneke G
Witte DR Witte Daniel R DR
Zgaga L Zgaga Lina L
Zitting P Zitting Paavo P
Beilby JP Beilby John P JP
James AL James Alan L AL
Kähönen M Kähönen Mika M
Lehtimäki T Lehtimäki Terho T
Nieminen MS Nieminen Markku S MS
Ohlsson C Ohlsson Claes C
Palmer LJ Palmer Lyle J LJ
Raitakari O Raitakari Olli O
Ridker PM Ridker Paul M PM
Stumvoll M Stumvoll Michael M
Tönjes A Tönjes Anke A
Viikari J Viikari Jorma J
Balkau B Balkau Beverley B
Ben-Shlomo Y Ben-Shlomo Yoav Y
Bergman RN Bergman Richard N RN
Boeing H Boeing Heiner H
Smith GD Smith George Davey GD
Ebrahim S Ebrahim Shah S
Froguel P Froguel Philippe P
Hansen T Hansen Torben T
Hengstenberg C Hengstenberg Christian C
Hveem K Hveem Kristian K
Isomaa B Isomaa Bo B
Jørgensen T Jørgensen Torben T
Karpe F Karpe Fredrik F
Khaw KT Khaw Kay-Tee KT
Laakso M Laakso Markku M
Lawlor DA Lawlor Debbie A DA
Marre M Marre Michel M
Meitinger T Meitinger Thomas T
Metspalu A Metspalu Andres A
Midthjell K Midthjell Kristian K
Pedersen O Pedersen Oluf O
Salomaa V Salomaa Veikko V
Schwarz PE Schwarz Peter E H PE
Tuomi T Tuomi Tiinamaija T
Tuomilehto J Tuomilehto Jaakko J
Valle TT Valle Timo T TT
Wareham NJ Wareham Nicholas J NJ
Arnold AM Arnold Alice M AM
Beckmann JS Beckmann Jacques S JS
Bergmann S Bergmann Sven S
Boerwinkle E Boerwinkle Eric E
Boomsma DI Boomsma Dorret I DI
Caulfield MJ Caulfield Mark J MJ
Collins FS Collins Francis S FS
Eiriksdottir G Eiriksdottir Gudny G
Gudnason V Gudnason Vilmundur V
Gyllensten U Gyllensten Ulf U
Hamsten A Hamsten Anders A
Hattersley AT Hattersley Andrew T AT
Hofman A Hofman Albert A
Hu FB Hu Frank B FB
Illig T Illig Thomas T
Iribarren C Iribarren Carlos C
Jarvelin MR Jarvelin Marjo-Riitta MR
Kao WH Kao W H Linda WH
Kaprio J Kaprio Jaakko J
Launer LJ Launer Lenore J LJ
Munroe PB Munroe Patricia B PB
Oostra B Oostra Ben B
Penninx BW Penninx Brenda W BW
Pramstaller PP Pramstaller Peter P PP
Psaty BM Psaty Bruce M BM
Quertermous T Quertermous Thomas T
Rissanen A Rissanen Aila A
Rudan I Rudan Igor I
Shuldiner AR Shuldiner Alan R AR
Soranzo N Soranzo Nicole N
Spector TD Spector Timothy D TD
Syvanen AC Syvanen Ann-Christine AC
Uda M Uda Manuela M
Uitterlinden A Uitterlinden André A
Völzke H Völzke Henry H
Vollenweider P Vollenweider Peter P
Wilson JF Wilson James F JF
Witteman JC Witteman Jacqueline C JC
Wright AF Wright Alan F AF
Abecasis GR Abecasis Gonçalo R GR
Boehnke M Boehnke Michael M
Borecki IB Borecki Ingrid B IB
Deloukas P Deloukas Panos P
Frayling TM Frayling Timothy M TM
Groop LC Groop Leif C LC
Haritunians T Haritunians Talin T
Hunter DJ Hunter David J DJ
Kaplan RC Kaplan Robert C RC
North KE North Kari E KE
O'Connell JR O'Connell Jeffrey R JR
Peltonen L Peltonen Leena L
Schlessinger D Schlessinger David D
Strachan DP Strachan David P DP
Hirschhorn JN Hirschhorn Joel N JN
Assimes TL Assimes Themistocles L TL
Wichmann HE Wichmann H-Erich HE
Thorsteinsdottir U Thorsteinsdottir Unnur U
van Duijn CM van Duijn Cornelia M CM
Stefansson K Stefansson Kari K
Cupples LA Cupples L Adrienne LA
Loos RJ Loos Ruth J F RJ
Barroso I Barroso Inês I
McCarthy MI McCarthy Mark I MI
Fox CS Fox Caroline S CS
Mohlke KL Mohlke Karen L KL
Lindgren CM Lindgren Cecilia M CM
INVESTIGATORS
JOURNAL
VOLUME: 42
ISSUE: 11
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2010
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
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UL1 RR025005 NCRR NIH HHS United States
UL1 RR025005-04 NCRR NIH HHS United States
UL1-RR025005 NCRR NIH HHS United States
Z01 HG000024-14 Intramural NIH HHS United States
­068545/Z/02 Wellcome Trust United Kingdom
­072960 Wellcome Trust United Kingdom
­076113/B/04/Z Wellcome Trust United Kingdom
­091746/Z/10/Z Wellcome Trust United Kingdom
­1RL1-MH083268-01 NIMH NIH HHS United States
­263-MA-410953 PHS HHS United States
­K23-DK080145 NIDDK NIH HHS United States
­K99HL094535 NHLBI NIH HHS United States
­MH084698 NIMH NIH HHS United States
­N01-AG-12100 NIA NIH HHS United States
­N01-HC-25195 NHLBI NIH HHS United States
­N01-HC-55019 NHLBI NIH HHS United States
­N01-HC-55020 NHLBI NIH HHS United States
­N01-HC-55021 NHLBI NIH HHS United States
­N01-HC-55022 NHLBI NIH HHS United States
­N01-HC15103 NHLBI NIH HHS United States
­N01-HC35129 NHLBI NIH HHS United States
­N01-HC45133 NHLBI NIH HHS United States
­N01-HC55015 NHLBI NIH HHS United States
­N01-HC55016 NHLBI NIH HHS United States
­N01-HC75150 NHLBI NIH HHS United States
­N01-HC85079 NHLBI NIH HHS United States
­N01-HC85080 NHLBI NIH HHS United States
­N01-HC85081 NHLBI NIH HHS United States
­N01-HC85082 NHLBI NIH HHS United States
­N01-HC85083 NHLBI NIH HHS United States
­N01-HC85084 NHLBI NIH HHS United States
­N01-HC85085 NHLBI NIH HHS United States
­N01-HC85086 NHLBI NIH HHS United States
­P30-DK072488 NIDDK NIH HHS United States
­R01-AG031890 NIA NIH HHS United States
­R01-DK-073490 NIDDK NIH HHS United States
­R01-DK075681 NIDDK NIH HHS United States
­R01-DK075787 NIDDK NIH HHS United States
­R01-HL086694 NHLBI NIH HHS United States
­R01-HL087641 NHLBI NIH HHS United States
­R01-HL087679 NHLBI NIH HHS United States
­R01-HL087700 NHLBI NIH HHS United States
­R01-HL088119 NHLBI NIH HHS United States
­R01-MH63706 NIMH NIH HHS United States
­R01­HL087652 NHLBI NIH HHS United States
­T32-HG00040 NHGRI NIH HHS United States
­U01-CA098233 NCI NIH HHS United States
­U01-DK062418 NIDDK NIH HHS United States
­U01-GM074518 NIGMS NIH HHS United States
­U01-HG004399 NHGRI NIH HHS United States
­U01-HG004402 NHGRI NIH HHS United States
­U01-HL084756 NHLBI NIH HHS United States
­UL1-RR025005 NCRR NIH HHS United States
­WT086596/Z/08/Z Wellcome Trust United Kingdom
British Heart Foundation United Kingdom
Department of Health United Kingdom
Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adipose Tissue anatomy & histology
Age Factors anatomy & histology
Chromosome Mapping anatomy & histology
Female anatomy & histology
Genome, Human anatomy & histology
Genome-Wide Association Study anatomy & histology
Humans anatomy & histology
Male anatomy & histology
Meta-Analysis as Topic anatomy & histology
Polymorphism, Single Nucleotide anatomy & histology
Sex Characteristics anatomy & histology
Waist-Hip Ratio anatomy & histology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3000924 NLM
UKMS33585 NLM