Sex-stratified Genome-wide Association Studies Including 270000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

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

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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
Original languageEnglish
Article numbere1003500
Pages (from-to)e1003500
JournalPLoS Genetics
Volume9
Issue number6
DOIs
Publication statusPublished - 2013

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    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., ... Heid, I. M. (2013). Sex-stratified Genome-wide Association Studies Including 270000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits. PLoS Genetics, 9(6), e1003500. [e1003500]. https://doi.org/10.1371/journal.pgen.1003500