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. Scherag; S. 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; Marjo-Riitta Jarvelin; Sirkka M. Keinanen-Kiukaanniemi; Inger Njølstad

doi:https://doi.org/10.1371/journal.pgen.1003500

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, Marjo-Riitta Jarvelin, Sirkka M. Keinanen-Kiukaanniemi, Inger Njølstad

Research output: Contribution to journal › Article › Academic › peer-review

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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(-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

Original language	English
Article number	e1003500
Pages (from-to)	e1003500
Journal	PLoS genetics
Volume	9
Issue number	6
DOIs	https://doi.org/10.1371/journal.pgen.1003500
Publication status	Published - 2013

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https://doi.org/10.1371/journal.pgen.1003500

Cite this

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

@article{f2f93fcbd0d041478317021c12c7006f,

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

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",

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

year = "2013",

doi = "https://doi.org/10.1371/journal.pgen.1003500",

language = "English",

volume = "9",

pages = "e1003500",

journal = "PLoS genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "6",

}

Randall, 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, JJ, Prokopenko, I, Waite, LL, Harris, TB, Smith, AV, Shuldiner, AR, McArdle, WL, Caulfield, MJ, Munroe, PB, Grönberg, H, Chen, YD, 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, BWJH, Hartikainen, AL, Järvelin, 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, Völzke, H, Kovacs, P, Tönjes, 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, HV, 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, SJ, Mateo Leach, I, 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, PE, 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, Krjuta Kov, K, Metspalu, A, Mihailov, E, Langenberg, C, Luan, J, Ong, KK, Chines, PS, Keinanen-Kiukaanniemie, S, Saaristo, TE, Edkins, S, Franks, PW, Hallmans, G, Shungin, D, Morris, AD, 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, JW, 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, AD, Kivimaki, M, Kumari, M, Assimes, TL, Barroso, I, Boehnke, M, Borecki, IB, Deloukas, P, Fox, CS, Frayling, TM, 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, RJ, Lindgren, CM, North, KE, Heid, IM, Jarvelin, M-R, Keinanen-Kiukaanniemi, SM & Njølstad, I 2013, 'Sex-stratified Genome-wide Association Studies Including 270000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits', PLoS genetics, vol. 9, no. 6, e1003500, pp. e1003500. https://doi.org/10.1371/journal.pgen.1003500

TY - JOUR

T1 - Sex-stratified Genome-wide Association Studies Including 270000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

AU - Randall, J.C.

AU - Winkler, T.W.

AU - Kutalik, Z.

AU - Berndt, S.I.

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PY - 2013

Y1 - 2013

N2 - 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

AB - 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

U2 - https://doi.org/10.1371/journal.pgen.1003500

DO - https://doi.org/10.1371/journal.pgen.1003500

M3 - Article

C2 - 23754948

SN - 1553-7390

VL - 9

SP - e1003500

JO - PLoS genetics

JF - PLoS genetics

IS - 6

M1 - e1003500

ER -