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

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Serval ID
serval:BIB_9D9E2CFE0188
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.
Journal
Plos Genetics
Author(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., Bonnefond A., Bonnefond A., Froguel P., 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.
Working group(s)
DIAGRAM Consortium, MAGIC Investigators
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2013
Volume
9
Number
6
Pages
e1003500
Language
english
Notes
Publication types: 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.
Publication Status: ppublish
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
03/10/2013 17:08
Last modification date
20/08/2019 15:04
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