A1 Journal article – refereed
Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits




List of Authors: Randall JC, Winkler TW, Kutalik Z, Berndt SI, Jackson AU, Monda KL, Kilpelainen TO, Esko T, Magi R, Li SX, Workalemahu T, Feitosa MF, Croteau-Chonka DC, Day FR, Fall T, Ferreira T, Gustafsson S, Locke AE, Mathieson I, Scherag A, Vedantam S, Wood AR, Liang LM, Steinthorsdottir V, Thorleifsson G, Dermitzakis ET, Dimas AS, Karpe F, Min JL, Nicholson G, Clegg DJ, Person T, Krohn JP, Bauer S, Buechler C, Eisinger K, Bonnefond A, Froguel P, Hottenga JJ, Prokopenko I, Waite LL, Harris TB, Smith AV, Shuldiner AR, McArdle WL, Caulfield MJ, Munroe PB, Gronberg H, Chen YDI, Li G, Beckmann JS, Johnson T, Thorsteinsdottir U, Teder-Laving M, Khaw KT, Wareham NJ, Zhao JH, Amin N, Oostra BA, Kraja AT, Province MA, Cupples LA, Heard-Costa NL, Kaprio J, Ripatti S, Surakka I, Collins FS, Saramies J, Tuomilehto J, Jula A, Salomaa V, Erdmann J, Hengstenberg C, Loley C, Schunkert H, Lamina C, Wichmann HE, Albrecht E, Gieger C, Hicks AA, Johansson A, Pramstaller PP, Kathiresan S, Speliotes EK, Penninx B, Hartikainen AL, Jarvelin MR, Gyllensten U, Boomsma DI, Campbell H, Wilson JF, Chanock SJ, Farrall M, Goel A, Medina-Gomez C, Rivadeneira F, Estrada K, Uitterlinden AG, Hofman A, Zillikens MC, den Heijer M, Kiemeney LA, Maschio A, Hall P, Tyrer J, Teumer A, Volzke H, Kovacs P, Tonjes A, Mangino M, Spector TD, Hayward C, Rudan I, Hall AS, Samani NJ, Attwood AP, Sambrook JG, Hung J, Palmer LJ, Lokki ML, Sinisalo J, Boucher G, Huikuri H, Lorentzon M, Ohlsson C, Eklund N, Eriksson JG, Barlassina C, Rivolta C, Nolte IM, Snieder H, Van der Klauw MM, Van Vliet-Ostaptchouk JV, Gejman PV, Shi JX, Jacobs KB, Wang ZM, Bakker SJL, Leach IM, Navis G, van der Harst P, Martin NG, Medland SE, Montgomery GW, Yang J, Chasman DI, Ridker PM, Rose LM, Lehtimaki T, Raitakari O, Absher D, Iribarren C, Basart H, Hovingh KG, Hypponen E, Power C, Anderson D, Beilby JP, Hui JN, Jolley J, Sager H, Bornstein SR, Schwarz PEH, Kristiansson K, Perola M, Lindstrom J, Swift AJ, Uusitupa M, Atalay M, Lakka TA, Rauramaa R, Bolton JL, Fowkes G, Fraser RM, Price JF, Fischer K, KrjutAikov K, Metspalu A, Mihailov E, Langenberg C, Luan JA, Ong KK, Chines PS, Keinanen-Kiukaanniemi SM, Saaristo TE, Edkins S, Franks PW, Hallmans G, Shungin D, Morris AD, Palmer CNA, Erbel R, Moebus S, Nothen MM, Pechlivanis S, Hveem K, Narisu N, Hamsten A, Humphries SE, Strawbridge RJ, Tremoli E, Grallert H, Thorand B, Illig T, Koenig W, Muller-Nurasyid M, Peters A, Boehm BO, Kleber ME, Marz W, Winkelmann BR, Kuusisto J, Laakso M, Arveiler D, Cesana G, Kuulasmaa K, Virtamo J, Yarnell JWG, Kuh D, Wong A, Lind L, de Faire U, Gigante B, Magnusson PKE, Pedersen NL, Dedoussis G, Dimitriou M, Kolovou G, Kanoni S, Stirrups K, Bonnycastle LL, Njolstad I, Wilsgaard T, Ganna A, Rehnberg E, Hingorani A, Kivimaki M, Kumari M, Assimes TL, Barroso IS, Boehnke M, Borecki IB, Deloukas P, Fox CS, Frayling T, Groop LC, Haritunians T, Hunter D, Ingelsson E, Kaplan R, Mohlke KL, O'Connell JR, Schlessinger D, Strachan DP, Stefansson K, van Duijn CM, Abecasis GR, McCarthy MI, Hirschhorn JN, Qi L, Loos RJF, Lindgren CM, North KE, Heid IM
Publisher: PUBLIC LIBRARY SCIENCE
Publication year: 2013
Journal: PLoS Genetics
Journal name in source: PLOS GENETICS
Journal acronym: PLOS GENET
Number in series: 6
Volume number: 9
Issue number: 6
ISSN: 1553-7390

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<5x10(-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.


Research Areas


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