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

Thursday,2013-09-12 13:20 America/Los_Angeles — eenright
TitleSex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.
Publication TypeJournal Article
Year of Publication2013
AuthorsRandall, JC, Winkler, TW, Kutalik, Z, Berndt, SI, Jackson, AU, Monda, KL, Kilpeläinen, TO, Esko, T, Mägi, R, Li, S, 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, L, 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, J-J, Prokopenko, I, Waite, LL, Harris, TB, Smith, AVernon, Shuldiner, AR, McArdle, WL, Caulfield, MJ, Munroe, PB, Grönberg, H, Chen, Y-DI, Li, G, Beckmann, JS, Johnson, T, Thorsteinsdottir, U, Teder-Laving, M, Khaw, K-T, Wareham, NJ, Zhao, JH, Amin, N, Oostra, BA, Kraja, AT, Province, MA, Cupples, AL, 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, EH, Albrecht, E, Gieger, C, Hicks, AA, Johansson, A, Pramstaller, PP, Kathiresan, S, Speliotes, EK, Penninx, B, Hartikainen, A-L, Jarvelin, M-R, Gyllensten, U, Boomsma, DI, Campbell, H, Wilson, JF, Chanock, SJ, Farrall, M, Goel, A, Medina-Gómez, C, Rivadeneira, F, Estrada, K, Uitterlinden, AG, Hofman, A, Zillikens, CM, Heijer, Mden, Kiemeney, LA, Maschio, A, Hall, P, Tyrer, J, Teumer, A, Völzke, H, Kovacs, P, Tönjes, A, Mangino, M, Spector, TD, Hayward, C, Rudan, I, Hall, AS, Samani, NJ, Attwood, APaul, Sambrook, JG, Hung, J, Palmer, LJ, Lokki, M-L, 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, J, Jacobs, KB, Wang, Z, Bakker, SJL, Leach, IMateo, Navis, G, van der Harst, P, Martin, NG, Medland, SE, Montgomery, GW, Yang, J, Chasman, DI, Ridker, PM, Rose, LM, Lehtimäki, T, Raitakari, O, Absher, D, Iribarren, C, Basart, H, Hovingh, KG, Hyppönen, E, Power, C, Anderson, D, Beilby, JP, Hui, J, Jolley, J, Sager, H, Bornstein, SR, Schwarz, PEH, Kristiansson, K, Perola, M, Lindström, J, Swift, AJ, Uusitupa, M, Atalay, M, Lakka, TA, Rauramaa, R, Bolton, JL, Fowkes, G, Fraser, RM, Price, JF, Fischer, K, Kov, KKrjutå, Metspalu, A, Mihailov, E, Langenberg, C, Luan, J'an, Ong, KK, Chines, PS, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Edkins, S, Franks, PW, Hallmans, G, Shungin, D, Morris, ADavid, Palmer, CNA, Erbel, R, Moebus, S, Nöthen, MM, Pechlivanis, S, Hveem, K, Narisu, N, Hamsten, A, Humphries, SE, Strawbridge, RJ, Tremoli, E, Grallert, H, Thorand, B, Illig, T, Koenig, W, Müller-Nurasyid, M, Peters, A, Boehm, BO, Kleber, ME, März, 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, Njølstad, I, Wilsgaard, T, Ganna, A, Rehnberg, E, Hingorani, A, Kivimaki, M, Kumari, M, Assimes, TL, Barroso, I, 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
Corporate/Institutional AuthorsDIAGRAM Consortium, MAGIC investigators
JournalPLoS Genet
Volume9
Issue6
Paginatione1003500
Date Published2013 Jun
ISSN1553-7404
KeywordsAnthropometry, Body Height, Body Mass Index, Body Weight, Body Weights and Measures, Female, Genetic Loci, Genome, Human, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Sex Characteristics, Waist Circumference, Waist-Hip Ratio
Abstract<p>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.</p>
DOI10.1371/journal.pgen.1003500
Alternate JournalPLoS Genet.
PubMed ID23754948
PubMed Central IDPMC3674993
Grant List090532/Z/09/Z / / Wellcome Trust / United Kingdom
UL1RR025005 / RR / NCRR NIH HHS / United States
M01RR16500 / RR / NCRR NIH HHS / United States
R01HS006516 / HS / AHRQ HHS / United States
083270 / / Wellcome Trust / United Kingdom
CZB/4/710 / / Chief Scientist Office / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
P01CA87969 / CA / NCI NIH HHS / United States
CZB/4/672 / / Chief Scientist Office / United Kingdom
G0000649 / / Medical Research Council / United Kingdom
R01AG004563 / AG / NIA NIH HHS / United States
N01AG12109 / AG / NIA NIH HHS / United States
UL1RR033176 / RR / NCRR NIH HHS / United States
P01 DK088761 / DK / NIDDK NIH HHS / United States
R01MH060870 / MH / NIMH NIH HHS / United States
069224 / / Wellcome Trust / United Kingdom
RG/08/008/25291 / / British Heart Foundation / United Kingdom
081682 / / Wellcome Trust / United Kingdom
N01HC85084 / HC / NHLBI NIH HHS / United States
R01AG028555 / AG / NIA NIH HHS / United States
268201100011C / / PHS HHS / United States
268201100005C / / PHS HHS / United States
089061/Z/09/Z / / Wellcome Trust / United Kingdom
084183/Z/07/Z / / Wellcome Trust / United Kingdom
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085301 / / Wellcome Trust / United Kingdom
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R01MH059588 / MH / NIMH NIH HHS / United States
079895 / / Wellcome Trust / United Kingdom
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RG2008/08 / RG / CSR NIH HHS / United States
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