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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PMID
23754948
TITLE
Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.
ABSTRACT
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<5×10(-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.
DATE PUBLISHED
2013 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
ppublish 2013/06
received 2012/05/04
accepted 2013/03/15
epublish 2013/06/06
entrez 2013/06/12 06:00
pubmed 2013/06/12 06:00
medline 2013/09/11 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Randall JC Randall Joshua C JC Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Winkler TW Winkler Thomas W TW
Kutalik Z Kutalik Zoltán Z
Berndt SI Berndt Sonja I SI
Jackson AU Jackson Anne U AU
Monda KL Monda Keri L KL
Kilpeläinen TO Kilpeläinen Tuomas O TO
Esko T Esko Tõnu T
Mägi R Mägi Reedik R
Li S Li Shengxu S
Workalemahu T Workalemahu Tsegaselassie T
Feitosa MF Feitosa Mary F MF
Croteau-Chonka DC Croteau-Chonka Damien C DC
Day FR Day Felix R FR
Fall T Fall Tove T
Ferreira T Ferreira Teresa T
Gustafsson S Gustafsson Stefan S
Locke AE Locke Adam E AE
Mathieson I Mathieson Iain I
Scherag A Scherag Andre A
Vedantam S Vedantam Sailaja S
Wood AR Wood Andrew R AR
Liang L Liang Liming L
Steinthorsdottir V Steinthorsdottir Valgerdur V
Thorleifsson G Thorleifsson Gudmar G
Dermitzakis ET Dermitzakis Emmanouil T ET
Dimas AS Dimas Antigone S AS
Karpe F Karpe Fredrik F
Min JL Min Josine L JL
Nicholson G Nicholson George G
Clegg DJ Clegg Deborah J DJ
Person T Person Thomas T
Krohn JP Krohn Jon P JP
Bauer S Bauer Sabrina S
Buechler C Buechler Christa C
Eisinger K Eisinger Kristina K
DIAGRAM Consortium
Bonnefond A Bonnefond Amélie A
Froguel P Froguel Philippe P
MAGIC Investigators
Hottenga JJ Hottenga Jouke-Jan JJ
Prokopenko I Prokopenko Inga I
Waite LL Waite Lindsay L LL
Harris TB Harris Tamara B TB
Smith AV Smith Albert Vernon AV
Shuldiner AR Shuldiner Alan R AR
McArdle WL McArdle Wendy L WL
Caulfield MJ Caulfield Mark J MJ
Munroe PB Munroe Patricia B PB
Grönberg H Grönberg Henrik H
Chen YD Chen Yii-Der Ida YD
Li G Li Guo G
Beckmann JS Beckmann Jacques S JS
Johnson T Johnson Toby T
Thorsteinsdottir U Thorsteinsdottir Unnur U
Teder-Laving M Teder-Laving Maris M
Khaw KT Khaw Kay-Tee KT
Wareham NJ Wareham Nicholas J NJ
Zhao JH Zhao Jing Hua JH
Amin N Amin Najaf N
Oostra BA Oostra Ben A BA
Kraja AT Kraja Aldi T AT
Province MA Province Michael A MA
Cupples LA Cupples L Adrienne LA
Heard-Costa NL Heard-Costa Nancy L NL
Kaprio J Kaprio Jaakko J
Ripatti S Ripatti Samuli S
Surakka I Surakka Ida I
Collins FS Collins Francis S FS
Saramies J Saramies Jouko J
Tuomilehto J Tuomilehto Jaakko J
Jula A Jula Antti A
Salomaa V Salomaa Veikko V
Erdmann J Erdmann Jeanette J
Hengstenberg C Hengstenberg Christian C
Loley C Loley Christina C
Schunkert H Schunkert Heribert H
Lamina C Lamina Claudia C
Wichmann HE Wichmann H Erich HE
Albrecht E Albrecht Eva E
Gieger C Gieger Christian C
Hicks AA Hicks Andrew A AA
Johansson A Johansson Asa A
Pramstaller PP Pramstaller Peter P PP
Kathiresan S Kathiresan Sekar S
Speliotes EK Speliotes Elizabeth K EK
Penninx B Penninx Brenda B
Hartikainen AL Hartikainen Anna-Liisa AL
Jarvelin MR Jarvelin Marjo-Riitta MR
Gyllensten U Gyllensten Ulf U
Boomsma DI Boomsma Dorret I DI
Campbell H Campbell Harry H
Wilson JF Wilson James F JF
Chanock SJ Chanock Stephen J SJ
Farrall M Farrall Martin M
Goel A Goel Anuj A
Medina-Gomez C Medina-Gomez Carolina C
Rivadeneira F Rivadeneira Fernando F
Estrada K Estrada Karol K
Uitterlinden AG Uitterlinden André G AG
Hofman A Hofman Albert A
Zillikens MC Zillikens M Carola MC
den Heijer M den Heijer Martin M
Kiemeney LA Kiemeney Lambertus A LA
Maschio A Maschio Andrea A
Hall P Hall Per P
Tyrer J Tyrer Jonathan J
Teumer A Teumer Alexander A
Völzke H Völzke Henry H
Kovacs P Kovacs Peter P
Tönjes A Tönjes Anke A
Mangino M Mangino Massimo M
Spector TD Spector Tim D TD
Hayward C Hayward Caroline C
Rudan I Rudan Igor I
Hall AS Hall Alistair S AS
Samani NJ Samani Nilesh J NJ
Attwood AP Attwood Antony Paul AP
Sambrook JG Sambrook Jennifer G JG
Hung J Hung Joseph J
Palmer LJ Palmer Lyle J LJ
Lokki ML Lokki Marja-Liisa ML
Sinisalo J Sinisalo Juha J
Boucher G Boucher Gabrielle G
Huikuri H Huikuri Heikki H
Lorentzon M Lorentzon Mattias M
Ohlsson C Ohlsson Claes C
Eklund N Eklund Niina N
Eriksson JG Eriksson Johan G JG
Barlassina C Barlassina Cristina C
Rivolta C Rivolta Carlo C
Nolte IM Nolte Ilja M IM
Snieder H Snieder Harold H
Van der Klauw MM Van der Klauw Melanie M MM
Van Vliet-Ostaptchouk JV Van Vliet-Ostaptchouk Jana V JV
Gejman PV Gejman Pablo V PV
Shi J Shi Jianxin J
Jacobs KB Jacobs Kevin B KB
Wang Z Wang Zhaoming Z
Bakker SJ Bakker Stephan J L SJ
Mateo Leach I Mateo Leach Irene I
Navis G Navis Gerjan G
van der Harst P van der Harst Pim P
Martin NG Martin Nicholas G NG
Medland SE Medland Sarah E SE
Montgomery GW Montgomery Grant W GW
Yang J Yang Jian J
Chasman DI Chasman Daniel I DI
Ridker PM Ridker Paul M PM
Rose LM Rose Lynda M LM
Lehtimäki T Lehtimäki Terho T
Raitakari O Raitakari Olli O
Absher D Absher Devin D
Iribarren C Iribarren Carlos C
Basart H Basart Hanneke H
Hovingh KG Hovingh Kees G KG
Hyppönen E Hyppönen Elina E
Power C Power Chris C
Anderson D Anderson Denise D
Beilby JP Beilby John P JP
Hui J Hui Jennie J
Jolley J Jolley Jennifer J
Sager H Sager Hendrik H
Bornstein SR Bornstein Stefan R SR
Schwarz PE Schwarz Peter E H PE
Kristiansson K Kristiansson Kati K
Perola M Perola Markus M
Lindström J Lindström Jaana J
Swift AJ Swift Amy J AJ
Uusitupa M Uusitupa Matti M
Atalay M Atalay Mustafa M
Lakka TA Lakka Timo A TA
Rauramaa R Rauramaa Rainer R
Bolton JL Bolton Jennifer L JL
Fowkes G Fowkes Gerry G
Fraser RM Fraser Ross M RM
Price JF Price Jackie F JF
Fischer K Fischer Krista K
Krjutå Kov K Krjutå Kov Kaarel K
Metspalu A Metspalu Andres A
Mihailov E Mihailov Evelin E
Langenberg C Langenberg Claudia C
Luan J Luan Jian'an J
Ong KK Ong Ken K KK
Chines PS Chines Peter S PS
Keinanen-Kiukaanniemi SM Keinanen-Kiukaanniemi Sirkka M SM
Saaristo TE Saaristo Timo E TE
Edkins S Edkins Sarah S
Franks PW Franks Paul W PW
Hallmans G Hallmans Göran G
Shungin D Shungin Dmitry D
Morris AD Morris Andrew David AD
Palmer CN Palmer Colin N A CN
Erbel R Erbel Raimund R
Moebus S Moebus Susanne S
Nöthen MM Nöthen Markus M MM
Pechlivanis S Pechlivanis Sonali S
Hveem K Hveem Kristian K
Narisu N Narisu Narisu N
Hamsten A Hamsten Anders A
Humphries SE Humphries Steve E SE
Strawbridge RJ Strawbridge Rona J RJ
Tremoli E Tremoli Elena E
Grallert H Grallert Harald H
Thorand B Thorand Barbara B
Illig T Illig Thomas T
Koenig W Koenig Wolfgang W
Müller-Nurasyid M Müller-Nurasyid Martina M
Peters A Peters Annette A
Boehm BO Boehm Bernhard O BO
Kleber ME Kleber Marcus E ME
März W März Winfried W
Winkelmann BR Winkelmann Bernhard R BR
Kuusisto J Kuusisto Johanna J
Laakso M Laakso Markku M
Arveiler D Arveiler Dominique D
Cesana G Cesana Giancarlo G
Kuulasmaa K Kuulasmaa Kari K
Virtamo J Virtamo Jarmo J
Yarnell JW Yarnell John W G JW
Kuh D Kuh Diana D
Wong A Wong Andrew A
Lind L Lind Lars L
de Faire U de Faire Ulf U
Gigante B Gigante Bruna B
Magnusson PK Magnusson Patrik K E PK
Pedersen NL Pedersen Nancy L NL
Dedoussis G Dedoussis George G
Dimitriou M Dimitriou Maria M
Kolovou G Kolovou Genovefa G
Kanoni S Kanoni Stavroula S
Stirrups K Stirrups Kathleen K
Bonnycastle LL Bonnycastle Lori L LL
Njølstad I Njølstad Inger I
Wilsgaard T Wilsgaard Tom T
Ganna A Ganna Andrea A
Rehnberg E Rehnberg Emil E
Hingorani A Hingorani Aroon A
Kivimaki M Kivimaki Mika M
Kumari M Kumari Meena M
Assimes TL Assimes Themistocles L TL
Barroso I Barroso Inês I
Boehnke M Boehnke Michael M
Borecki IB Borecki Ingrid B IB
Deloukas P Deloukas Panos P
Fox CS Fox Caroline S CS
Frayling T Frayling Timothy T
Groop LC Groop Leif C LC
Haritunians T Haritunians Talin T
Hunter D Hunter David D
Ingelsson E Ingelsson Erik E
Kaplan R Kaplan Robert R
Mohlke KL Mohlke Karen L KL
O'Connell JR O'Connell Jeffrey R JR
Schlessinger D Schlessinger David D
Strachan DP Strachan David P DP
Stefansson K Stefansson Kari K
van Duijn CM van Duijn Cornelia M CM
Abecasis GR Abecasis Gonçalo R GR
McCarthy MI McCarthy Mark I MI
Hirschhorn JN Hirschhorn Joel N JN
Qi L Qi Lu L
Loos RJ Loos Ruth J F RJ
Lindgren CM Lindgren Cecilia M CM
North KE North Kari E KE
Heid IM Heid Iris M IM
INVESTIGATORS
JOURNAL
VOLUME: 9
ISSUE: 6
TITLE: PLoS genetics
ISOABBREVIATION: PLoS Genet.
YEAR: 2013
MONTH: Jun
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1553-7404
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS Genet
COUNTRY: United States
ISSNLINKING: 1553-7390
NLMUNIQUEID: 101239074
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Anthropometry methods
Body Height genetics
Body Mass Index genetics
Body Weight genetics
Body Weights and Measures genetics
Female genetics
Genetic Loci genetics
Genome, Human genetics
Genome-Wide Association Study genetics
Humans genetics
Male genetics
Polymorphism, Single Nucleotide genetics
Sex Characteristics genetics
Waist Circumference genetics
Waist-Hip Ratio genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3674993 NLM