Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

Autoria(s): Randall J.C.; Winkler T.W.; Kutalik Z.; Berndt S.I.; Jackson A.U.; Monda K.L.; Kilpeläinen T.O.; Esko T.; Mägi R.; Li S.; Workalemahu T.; Feitosa M.F.; Croteau-Chonka D.C.; Day F.R.; Fall T.; Ferreira T.; Gustafsson S.; Locke A.E.; Mathieson I.; Scherag A.; Vedantam S.; Wood A.R.; Liang L.; Steinthorsdottir V.; Thorleifsson G.; Dermitzakis E.T.; Dimas A.S.; Karpe F.; Min J.L.; Nicholson G.; Clegg D.J.; Person T.; Krohn J.P.; Bauer S.; Buechler C.; Eisinger K.; DIAGRAM Consortium; Bonnefond A.; Bonnefond A.; Froguel P.; MAGIC Investigators; Hottenga J.J.; Hottenga J.J.; Prokopenko I.; Waite L.L.; Harris T.B.; Smith A.V.; Shuldiner A.R.; McArdle W.L.; Caulfield M.J.; Munroe P.B.; Grönberg H.; Chen Y.D.; Li G.; Beckmann J.S.; Johnson T.; Thorsteinsdottir U.; Teder-Laving M.; Khaw K.T.; Wareham N.J.; Zhao J.H.; Amin N.; Oostra B.A.; Kraja A.T.; Province M.A.; Cupples L.A.; Heard-Costa N.L.; Kaprio J.; Ripatti S.; Surakka I.; Collins F.S.; Saramies J.; Tuomilehto J.; Jula A.; Salomaa V.; Erdmann J.; Hengstenberg C.; Loley C.; Schunkert H.; Lamina C.; Wichmann H.E.; Albrecht E.; Gieger C.; Hicks A.A.; Johansson A.; Pramstaller P.P.; Kathiresan S.; Speliotes E.K.; Penninx B.; Hartikainen A.L.; Jarvelin M.R.; Gyllensten U.; Boomsma D.I.; Campbell H.; Wilson J.F.; Chanock S.J.; Farrall M.; Goel A.; Medina-Gomez C.; Rivadeneira F.; Estrada K.; Uitterlinden A.G.; Hofman A.; Zillikens M.C.; den Heijer M.; Kiemeney L.A.; Maschio A.; Hall P.; Tyrer J.; Teumer A.; Völzke H.; Kovacs P.; Tönjes A.; Mangino M.; Spector T.D.; Hayward C.; Rudan I.; Hall A.S.; Samani N.J.; Attwood A.P.; Sambrook J.G.; Hung J.; Palmer L.J.; Lokki M.L.; Sinisalo J.; Boucher G.; Huikuri H.; Lorentzon M.; Ohlsson C.; Eklund N.; Eriksson J.G.; Barlassina C.; Rivolta C.; Nolte I.M.; Snieder H.; Van der Klauw M.M.; Van Vliet-Ostaptchouk J.V.; Gejman P.V.; Shi J.; Jacobs K.B.; Wang Z.; Bakker S.J.; Mateo Leach I.; Navis G.; van der Harst P.; Martin N.G.; Medland S.E.; Montgomery G.W.; Yang J.; Chasman D.I.; Ridker P.M.; Rose L.M.; Lehtimäki T.; Raitakari O.; Absher D.; Iribarren C.; Basart H.; Hovingh K.G.; Hyppönen E.; Power C.; Anderson D.; Beilby J.P.; Hui J.; Jolley J.; Sager H.; Bornstein S.R.; Schwarz P.E.; Kristiansson K.; Perola M.; Lindström J.; Swift A.J.; Uusitupa M.; Atalay M.; Lakka T.A.; Rauramaa R.; Bolton J.L.; Fowkes G.; Fraser R.M.; Price J.F.; Fischer K.; Krjutå Kov K.; Metspalu A.; Mihailov E.; Langenberg C.; Luan J.; Ong K.K.; Chines P.S.; Keinanen-Kiukaanniemi S.M.; Saaristo T.E.; Edkins S.; Franks P.W.; Hallmans G.; Shungin D.; Morris A.D.; Palmer C.N.; Erbel R.; Moebus S.; Nöthen M.M.; Pechlivanis S.; Hveem K.; Narisu N.; Hamsten A.; Humphries S.E.; Strawbridge R.J.; Tremoli E.; Grallert H.; Thorand B.; Illig T.; Koenig W.; Müller-Nurasyid M.; Peters A.; Boehm B.O.; Kleber M.E.; März W.; Winkelmann B.R.; Kuusisto J.; Laakso M.; Arveiler D.; Cesana G.; Kuulasmaa K.; Virtamo J.; Yarnell J.W.; Kuh D.; Wong A.; Lind L.; de Faire U.; Gigante B.; Magnusson P.K.; Pedersen N.L.; Dedoussis G.; Dimitriou M.; Kolovou G.; Kanoni S.; Stirrups K.; Bonnycastle L.L.; Njølstad I.; Wilsgaard T.; Ganna A.; Rehnberg E.; Hingorani A.; Kivimaki M.; Kumari M.; Assimes T.L.; Barroso I.; Boehnke M.; Borecki I.B.; Deloukas P.; Fox C.S.; Frayling T.; Groop L.C.; Haritunians T.; Hunter D.; Ingelsson E.; Kaplan R.; Mohlke K.L.; O'Connell J.R.; Schlessinger D.; Strachan D.P.; Stefansson K.; van Duijn C.M.; Abecasis G.R.; McCarthy M.I.; Hirschhorn J.N.; Qi L.; Loos R.J.; Lindgren C.M.; North K.E.; Heid I.M.
Data(s)

2013
Resumo

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.
Identificador

https://serval.unil.ch/?id=serval:BIB_9D9E2CFE0188

isbn:1553-7404 (Electronic)

pmid:23754948

doi:10.1371/journal.pgen.1003500

isiid:000321222600005

http://my.unil.ch/serval/document/BIB_9D9E2CFE0188.pdf

http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_9D9E2CFE01884
Idioma(s)

en
Direitos

info:eu-repo/semantics/openAccess
Fonte

Plos Genetics, vol. 9, no. 6, pp. e1003500
Palavras-Chave #Anthropometry/methods; Body Height/genetics; Body Mass Index; Body Weight/genetics; Body Weights and Measures; Female; Genetic Loci; Genome, Human; Genome-Wide Association Study; Humans; Male; Polymorphism, Single Nucleotide; Sex Characteristics; Waist Circumference/genetics; Waist-Hip Ratio
Tipo

info:eu-repo/semantics/article

article
Acesso ao item digital