Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/32663
Title: Sex-stratified genoSex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits
Authors: 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.
Froguel, P.
MAGIC Investigators
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.
First Published: 6-Jun-2013
Publisher: Public Library of Science
Citation: PLoS Genetics, 2013, 9 (6), e1003500
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.
DOI Link: 10.1371/journal.pgen.1003500
ISSN: 1553-7390
eISSN: 1553-7404
Links: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003500
http://hdl.handle.net/2381/32663
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences



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