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

Joshua C. Randall, Thomas W. Winkler, Zoltán Kutalik, Sonja I. Berndt, Anne U. Jackson, Keri L. Monda, Tuomas O. Kilpeläinen, Tõnu Esko, Reedik Mägi, Shengxu Li, Tsegaselassie Workalemahu, Mary F. Feitosa, Damien C. Croteau-Chonka, Felix R. Day, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Adam E. Locke, Iain Mathieson, Andre Scherag & 244 others Sailaja Vedantam, Andrew R. Wood, Liming Liang, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Emmanouil T. Dermitzakis, Antigone S. Dimas, Fredrik Karpe, Josine L. Min, George Nicholson, Deborah J. Clegg, Thomas Person, Jon P. Krohn, Sabrina Bauer, Christa Buechler, Kristina Eisinger, Amélie Bonnefond, Philippe Froguel, Jouke Jan Hottenga, Inga Prokopenko, Lindsay L. Waite, Tamara B. Harris, Albert Vernon Smith, Alan R. Shuldiner, Wendy L. McArdle, Mark J. Caulfield, Patricia B. Munroe, Henrik Grönberg, Yii Der Ida Chen, Guo Li, Jacques S. Beckmann, Toby Johnson, Unnur Thorsteinsdottir, Maris Teder-Laving, Kay Tee Khaw, Nicholas J. Wareham, Jing Hua Zhao, Najaf Amin, Ben A. Oostra, Aldi T. Kraja, Michael A. Province, L. Adrienne Cupples, Nancy L. Heard-Costa, Jaakko Kaprio, Samuli Ripatti, Ida Surakka, Francis S. Collins, Jouko Saramies, Jaakko Tuomilehto, Antti Jula, Veikko Salomaa, Jeanette Erdmann, Christian Hengstenberg, Christina Loley, Heribert Schunkert, Claudia Lamina, H. Erich Wichmann, Eva Albrecht, Christian Gieger, Andrew A. Hicks, Åsa Johansson, Peter P. Pramstaller, Sekar Kathiresan, Elizabeth K. Speliotes, Brenda Penninx, Anna Liisa Hartikainen, Marjo Riitta Jarvelin, Ulf Gyllensten, Dorret I. Boomsma, Harry Campbell, James F. Wilson, Stephen J. Chanock, Martin Farrall, Anuj Goel, Carolina Medina-Gomez, Fernando Rivadeneira, Karol Estrada, André G. Uitterlinden, Albert Hofman, M. Carola Zillikens, Martin den Heijer, Lambertus A. Kiemeney, Andrea Maschio, Per Hall, Jonathan Tyrer, Alexander Teumer, Henry Völzke, Peter Kovacs, Anke Tönjes, Massimo Mangino, Tim D. Spector, Caroline Hayward, Igor Rudan, Alistair S. Hall, Nilesh J. Samani, Antony Paul Attwood, Jennifer G. Sambrook, Joseph Hung, Lyle J. Palmer, Marja Liisa Lokki, Juha Sinisalo, Gabrielle Boucher, Heikki Huikuri, Mattias Lorentzon, Claes Ohlsson, Niina Eklund, Johan G. Eriksson, Cristina Barlassina, Carlo Rivolta, Ilja M. Nolte, Harold Snieder, Melanie M. van der Klauw, Jana V. van Vliet-Ostaptchouk, Pablo V. Gejman, Jianxin Shi, Kevin B. Jacobs, Zhaoming Wang, Stephan J L Bakker, Irene Mateo Leach, Gerjan Navis, Pim van der Harst, Nicholas G. Martin, Sarah E. Medland, Grant W. Montgomery, Jian Yang, Daniel I. Chasman, Paul M. Ridker, Lynda M. Rose, Terho Lehtimäki, Olli Raitakari, Devin Absher, Carlos Iribarren, Hanneke Basart, Kees G. Hovingh, Elina Hyppönen, Chris Power, Denise Anderson, John P. Beilby, Jennie Hui, Jennifer Jolley, Hendrik Sager, Stefan R. Bornstein, Peter E H Schwarz, Kati Kristiansson, Markus Perola, Jaana Lindström, Amy J. Swift, Matti Uusitupa, Mustafa Atalay, Timo A. Lakka, Rainer Rauramaa, Jennifer L. Bolton, Gerry Fowkes, Ross M. Fraser, Jackie F. Price, Krista Fischer, Kaarel KrjutÅkov, Andres Metspalu, Evelin Mihailov, Claudia Langenberg, Jian'an Luan, Ken K. Ong, Peter S. Chines, Sirkka M. Keinanen-Kiukaanniemi, Timo E. Saaristo, Sarah Edkins, Paul W. Franks, Göran Hallmans, Dmitry Shungin, Andrewvid da Morris, Colin N A Palmer, Raimund Erbel, Susanne Moebus, Markus M. Nöthen, Sonali Pechlivanis, Kristian Hveem, Narisu Narisu, Anders Hamsten, Steve E. Humphries, Rona J. Strawbridge, Elena Tremoli, Harald Grallert, Barbara Thorand, Thomas Illig, Wolfgang Koenig, Martina Müller-Nurasyid, Annette Peters, Bernhard O. Boehm, Marcus E. Kleber, Winfried März, Bernhard R. Winkelmann, Johanna Kuusisto, Markku Laakso, Dominique Arveiler, Giancarlo Cesana, Kari Kuulasmaa, Jarmo Virtamo, John W G Yarnell, Diana Kuh, Andrew Wong, Lars Lind, Ulf de Faire, Bruna Gigante, Patrik K E Magnusson, Nancy L. Pedersen, George Dedoussis, Maria Dimitriou, Genovefa Kolovou, Stavroula Kanoni, Kathleen Stirrups, Lori L. Bonnycastle, Inger Njølstad, Tom Wilsgaard, Andrea Ganna, Emil Rehnberg, Aroon Hingorani, Mika Kivimaki, Meena Kumari, Themistocles L. Assimes, Inês Barroso, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Caroline S. Fox, Timothy Frayling, Leif C. Groop, Talin Haritunians, David Hunter, Erik Ingelsson, Robert C. Kaplan, Karen L. Mohlke, Jeffrey R. O'Connell, David Schlessinger, David P. Strachan, Kari Stefansson, Cornelia M. van Duijn, Gonçalo R. Abecasis, Mark I. McCarthy, Joel N. Hirschhorn, Lu Qi, Ruth J F Loos, Cecilia M. Lindgren, Kari E. North, Iris M. Heid

Research output: Contribution to journalArticle

180 Citations (Scopus)

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 languageEnglish (US)
Article numbere1003500
JournalPLoS Genetics
Volume9
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Genetic Loci
Genome-Wide Association Study
sexual dimorphism
Sex Characteristics
genome
gender differences
loci
Hip
gender
hips
Genome
Weights and Measures
Waist-Hip Ratio
diabetes
Waist Circumference
Genetic Therapy
waist-to-hip ratio
body mass
Single Nucleotide Polymorphism
waist

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Randall, J. C., Winkler, T. W., Kutalik, Z., Berndt, S. I., Jackson, A. U., Monda, K. L., ... Heid, I. M. (2013). Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits. PLoS Genetics, 9(6), [e1003500]. https://doi.org/10.1371/journal.pgen.1003500

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits. / Randall, Joshua C.; Winkler, Thomas W.; Kutalik, Zoltán; Berndt, Sonja I.; Jackson, Anne U.; Monda, Keri L.; Kilpeläinen, Tuomas O.; Esko, Tõnu; Mägi, Reedik; Li, Shengxu; Workalemahu, Tsegaselassie; Feitosa, Mary F.; Croteau-Chonka, Damien C.; Day, Felix R.; Fall, Tove; Ferreira, Teresa; Gustafsson, Stefan; Locke, Adam E.; Mathieson, Iain; Scherag, Andre; Vedantam, Sailaja; Wood, Andrew R.; Liang, Liming; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Karpe, Fredrik; Min, Josine L.; Nicholson, George; Clegg, Deborah J.; Person, Thomas; Krohn, Jon P.; Bauer, Sabrina; Buechler, Christa; Eisinger, Kristina; Bonnefond, Amélie; Froguel, Philippe; Hottenga, Jouke Jan; Prokopenko, Inga; Waite, Lindsay L.; Harris, Tamara B.; Smith, Albert Vernon; Shuldiner, Alan R.; McArdle, Wendy L.; Caulfield, Mark J.; Munroe, Patricia B.; Grönberg, Henrik; Chen, Yii Der Ida; Li, Guo; Beckmann, Jacques S.; Johnson, Toby; Thorsteinsdottir, Unnur; Teder-Laving, Maris; Khaw, Kay Tee; Wareham, Nicholas J.; Zhao, Jing Hua; Amin, Najaf; Oostra, Ben A.; Kraja, Aldi T.; Province, Michael A.; Cupples, L. Adrienne; Heard-Costa, Nancy L.; Kaprio, Jaakko; Ripatti, Samuli; Surakka, Ida; Collins, Francis S.; Saramies, Jouko; Tuomilehto, Jaakko; Jula, Antti; Salomaa, Veikko; Erdmann, Jeanette; Hengstenberg, Christian; Loley, Christina; Schunkert, Heribert; Lamina, Claudia; Wichmann, H. Erich; Albrecht, Eva; Gieger, Christian; Hicks, Andrew A.; Johansson, Åsa; Pramstaller, Peter P.; Kathiresan, Sekar; Speliotes, Elizabeth K.; Penninx, Brenda; Hartikainen, Anna Liisa; Jarvelin, Marjo Riitta; Gyllensten, Ulf; Boomsma, Dorret I.; Campbell, Harry; Wilson, James F.; Chanock, Stephen J.; Farrall, Martin; Goel, Anuj; Medina-Gomez, Carolina; Rivadeneira, Fernando; Estrada, Karol; Uitterlinden, André G.; Hofman, Albert; Zillikens, M. Carola; den Heijer, Martin; Kiemeney, Lambertus A.; Maschio, Andrea; Hall, Per; Tyrer, Jonathan; Teumer, Alexander; Völzke, Henry; Kovacs, Peter; Tönjes, Anke; Mangino, Massimo; Spector, Tim D.; Hayward, Caroline; Rudan, Igor; Hall, Alistair S.; Samani, Nilesh J.; Attwood, Antony Paul; Sambrook, Jennifer G.; Hung, Joseph; Palmer, Lyle J.; Lokki, Marja Liisa; Sinisalo, Juha; Boucher, Gabrielle; Huikuri, Heikki; Lorentzon, Mattias; Ohlsson, Claes; Eklund, Niina; Eriksson, Johan G.; Barlassina, Cristina; Rivolta, Carlo; Nolte, Ilja M.; Snieder, Harold; van der Klauw, Melanie M.; van Vliet-Ostaptchouk, Jana V.; Gejman, Pablo V.; Shi, Jianxin; Jacobs, Kevin B.; Wang, Zhaoming; Bakker, Stephan J L; Mateo Leach, Irene; Navis, Gerjan; van der Harst, Pim; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Yang, Jian; Chasman, Daniel I.; Ridker, Paul M.; Rose, Lynda M.; Lehtimäki, Terho; Raitakari, Olli; Absher, Devin; Iribarren, Carlos; Basart, Hanneke; Hovingh, Kees G.; Hyppönen, Elina; Power, Chris; Anderson, Denise; Beilby, John P.; Hui, Jennie; Jolley, Jennifer; Sager, Hendrik; Bornstein, Stefan R.; Schwarz, Peter E H; Kristiansson, Kati; Perola, Markus; Lindström, Jaana; Swift, Amy J.; Uusitupa, Matti; Atalay, Mustafa; Lakka, Timo A.; Rauramaa, Rainer; Bolton, Jennifer L.; Fowkes, Gerry; Fraser, Ross M.; Price, Jackie F.; Fischer, Krista; KrjutÅkov, Kaarel; Metspalu, Andres; Mihailov, Evelin; Langenberg, Claudia; Luan, Jian'an; Ong, Ken K.; Chines, Peter S.; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Edkins, Sarah; Franks, Paul W.; Hallmans, Göran; Shungin, Dmitry; da Morris, Andrewvid; Palmer, Colin N A; Erbel, Raimund; Moebus, Susanne; Nöthen, Markus M.; Pechlivanis, Sonali; Hveem, Kristian; Narisu, Narisu; Hamsten, Anders; Humphries, Steve E.; Strawbridge, Rona J.; Tremoli, Elena; Grallert, Harald; Thorand, Barbara; Illig, Thomas; Koenig, Wolfgang; Müller-Nurasyid, Martina; Peters, Annette; Boehm, Bernhard O.; Kleber, Marcus E.; März, Winfried; Winkelmann, Bernhard R.; Kuusisto, Johanna; Laakso, Markku; Arveiler, Dominique; Cesana, Giancarlo; Kuulasmaa, Kari; Virtamo, Jarmo; Yarnell, John W G; Kuh, Diana; Wong, Andrew; Lind, Lars; de Faire, Ulf; Gigante, Bruna; Magnusson, Patrik K E; Pedersen, Nancy L.; Dedoussis, George; Dimitriou, Maria; Kolovou, Genovefa; Kanoni, Stavroula; Stirrups, Kathleen; Bonnycastle, Lori L.; Njølstad, Inger; Wilsgaard, Tom; Ganna, Andrea; Rehnberg, Emil; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena; Assimes, Themistocles L.; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Frayling, Timothy; Groop, Leif C.; Haritunians, Talin; Hunter, David; Ingelsson, Erik; Kaplan, Robert C.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Schlessinger, David; Strachan, David P.; Stefansson, Kari; van Duijn, Cornelia M.; Abecasis, Gonçalo R.; McCarthy, Mark I.; Hirschhorn, Joel N.; Qi, Lu; Loos, Ruth J F; Lindgren, Cecilia M.; North, Kari E.; Heid, Iris M.

In: PLoS Genetics, Vol. 9, No. 6, e1003500, 06.2013.

Research output: Contribution to journalArticle

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, 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, Å, 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, 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, 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, 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, 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, KrjutÅkov, K, Metspalu, A, Mihailov, E, Langenberg, C, Luan, J, Ong, KK, Chines, PS, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Edkins, S, Franks, PW, Hallmans, G, Shungin, D, da Morris, A, 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, RC, 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 2013, 'Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits', PLoS Genetics, vol. 9, no. 6, e1003500. https://doi.org/10.1371/journal.pgen.1003500
Randall, Joshua C. ; Winkler, Thomas W. ; Kutalik, Zoltán ; Berndt, Sonja I. ; Jackson, Anne U. ; Monda, Keri L. ; Kilpeläinen, Tuomas O. ; Esko, Tõnu ; Mägi, Reedik ; Li, Shengxu ; Workalemahu, Tsegaselassie ; Feitosa, Mary F. ; Croteau-Chonka, Damien C. ; Day, Felix R. ; Fall, Tove ; Ferreira, Teresa ; Gustafsson, Stefan ; Locke, Adam E. ; Mathieson, Iain ; Scherag, Andre ; Vedantam, Sailaja ; Wood, Andrew R. ; Liang, Liming ; Steinthorsdottir, Valgerdur ; Thorleifsson, Gudmar ; Dermitzakis, Emmanouil T. ; Dimas, Antigone S. ; Karpe, Fredrik ; Min, Josine L. ; Nicholson, George ; Clegg, Deborah J. ; Person, Thomas ; Krohn, Jon P. ; Bauer, Sabrina ; Buechler, Christa ; Eisinger, Kristina ; Bonnefond, Amélie ; Froguel, Philippe ; Hottenga, Jouke Jan ; Prokopenko, Inga ; Waite, Lindsay L. ; Harris, Tamara B. ; Smith, Albert Vernon ; Shuldiner, Alan R. ; McArdle, Wendy L. ; Caulfield, Mark J. ; Munroe, Patricia B. ; Grönberg, Henrik ; Chen, Yii Der Ida ; Li, Guo ; Beckmann, Jacques S. ; Johnson, Toby ; Thorsteinsdottir, Unnur ; Teder-Laving, Maris ; Khaw, Kay Tee ; Wareham, Nicholas J. ; Zhao, Jing Hua ; Amin, Najaf ; Oostra, Ben A. ; Kraja, Aldi T. ; Province, Michael A. ; Cupples, L. Adrienne ; Heard-Costa, Nancy L. ; Kaprio, Jaakko ; Ripatti, Samuli ; Surakka, Ida ; Collins, Francis S. ; Saramies, Jouko ; Tuomilehto, Jaakko ; Jula, Antti ; Salomaa, Veikko ; Erdmann, Jeanette ; Hengstenberg, Christian ; Loley, Christina ; Schunkert, Heribert ; Lamina, Claudia ; Wichmann, H. Erich ; Albrecht, Eva ; Gieger, Christian ; Hicks, Andrew A. ; Johansson, Åsa ; Pramstaller, Peter P. ; Kathiresan, Sekar ; Speliotes, Elizabeth K. ; Penninx, Brenda ; Hartikainen, Anna Liisa ; Jarvelin, Marjo Riitta ; Gyllensten, Ulf ; Boomsma, Dorret I. ; Campbell, Harry ; Wilson, James F. ; Chanock, Stephen J. ; Farrall, Martin ; Goel, Anuj ; Medina-Gomez, Carolina ; Rivadeneira, Fernando ; Estrada, Karol ; Uitterlinden, André G. ; Hofman, Albert ; Zillikens, M. Carola ; den Heijer, Martin ; Kiemeney, Lambertus A. ; Maschio, Andrea ; Hall, Per ; Tyrer, Jonathan ; Teumer, Alexander ; Völzke, Henry ; Kovacs, Peter ; Tönjes, Anke ; Mangino, Massimo ; Spector, Tim D. ; Hayward, Caroline ; Rudan, Igor ; Hall, Alistair S. ; Samani, Nilesh J. ; Attwood, Antony Paul ; Sambrook, Jennifer G. ; Hung, Joseph ; Palmer, Lyle J. ; Lokki, Marja Liisa ; Sinisalo, Juha ; Boucher, Gabrielle ; Huikuri, Heikki ; Lorentzon, Mattias ; Ohlsson, Claes ; Eklund, Niina ; Eriksson, Johan G. ; Barlassina, Cristina ; Rivolta, Carlo ; Nolte, Ilja M. ; Snieder, Harold ; van der Klauw, Melanie M. ; van Vliet-Ostaptchouk, Jana V. ; Gejman, Pablo V. ; Shi, Jianxin ; Jacobs, Kevin B. ; Wang, Zhaoming ; Bakker, Stephan J L ; Mateo Leach, Irene ; Navis, Gerjan ; van der Harst, Pim ; Martin, Nicholas G. ; Medland, Sarah E. ; Montgomery, Grant W. ; Yang, Jian ; Chasman, Daniel I. ; Ridker, Paul M. ; Rose, Lynda M. ; Lehtimäki, Terho ; Raitakari, Olli ; Absher, Devin ; Iribarren, Carlos ; Basart, Hanneke ; Hovingh, Kees G. ; Hyppönen, Elina ; Power, Chris ; Anderson, Denise ; Beilby, John P. ; Hui, Jennie ; Jolley, Jennifer ; Sager, Hendrik ; Bornstein, Stefan R. ; Schwarz, Peter E H ; Kristiansson, Kati ; Perola, Markus ; Lindström, Jaana ; Swift, Amy J. ; Uusitupa, Matti ; Atalay, Mustafa ; Lakka, Timo A. ; Rauramaa, Rainer ; Bolton, Jennifer L. ; Fowkes, Gerry ; Fraser, Ross M. ; Price, Jackie F. ; Fischer, Krista ; KrjutÅkov, Kaarel ; Metspalu, Andres ; Mihailov, Evelin ; Langenberg, Claudia ; Luan, Jian'an ; Ong, Ken K. ; Chines, Peter S. ; Keinanen-Kiukaanniemi, Sirkka M. ; Saaristo, Timo E. ; Edkins, Sarah ; Franks, Paul W. ; Hallmans, Göran ; Shungin, Dmitry ; da Morris, Andrewvid ; Palmer, Colin N A ; Erbel, Raimund ; Moebus, Susanne ; Nöthen, Markus M. ; Pechlivanis, Sonali ; Hveem, Kristian ; Narisu, Narisu ; Hamsten, Anders ; Humphries, Steve E. ; Strawbridge, Rona J. ; Tremoli, Elena ; Grallert, Harald ; Thorand, Barbara ; Illig, Thomas ; Koenig, Wolfgang ; Müller-Nurasyid, Martina ; Peters, Annette ; Boehm, Bernhard O. ; Kleber, Marcus E. ; März, Winfried ; Winkelmann, Bernhard R. ; Kuusisto, Johanna ; Laakso, Markku ; Arveiler, Dominique ; Cesana, Giancarlo ; Kuulasmaa, Kari ; Virtamo, Jarmo ; Yarnell, John W G ; Kuh, Diana ; Wong, Andrew ; Lind, Lars ; de Faire, Ulf ; Gigante, Bruna ; Magnusson, Patrik K E ; Pedersen, Nancy L. ; Dedoussis, George ; Dimitriou, Maria ; Kolovou, Genovefa ; Kanoni, Stavroula ; Stirrups, Kathleen ; Bonnycastle, Lori L. ; Njølstad, Inger ; Wilsgaard, Tom ; Ganna, Andrea ; Rehnberg, Emil ; Hingorani, Aroon ; Kivimaki, Mika ; Kumari, Meena ; Assimes, Themistocles L. ; Barroso, Inês ; Boehnke, Michael ; Borecki, Ingrid B. ; Deloukas, Panos ; Fox, Caroline S. ; Frayling, Timothy ; Groop, Leif C. ; Haritunians, Talin ; Hunter, David ; Ingelsson, Erik ; Kaplan, Robert C. ; Mohlke, Karen L. ; O'Connell, Jeffrey R. ; Schlessinger, David ; Strachan, David P. ; Stefansson, Kari ; van Duijn, Cornelia M. ; Abecasis, Gonçalo R. ; McCarthy, Mark I. ; Hirschhorn, Joel N. ; Qi, Lu ; Loos, Ruth J F ; Lindgren, Cecilia M. ; North, Kari E. ; Heid, Iris M. / Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits. In: PLoS Genetics. 2013 ; Vol. 9, No. 6.
@article{e23e99d3fe4b4880a660695b7c67db0e,
title = "Sex-stratified Genome-wide Association Studies Including 270,000 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 = "Randall, {Joshua C.} and Winkler, {Thomas W.} and Zolt{\'a}n Kutalik and Berndt, {Sonja I.} and Jackson, {Anne U.} and Monda, {Keri L.} and Kilpel{\"a}inen, {Tuomas O.} and T{\~o}nu Esko and Reedik M{\"a}gi and Shengxu Li and Tsegaselassie Workalemahu and Feitosa, {Mary F.} and Croteau-Chonka, {Damien C.} and Day, {Felix R.} and Tove Fall and Teresa Ferreira and Stefan Gustafsson and Locke, {Adam E.} and Iain Mathieson and Andre Scherag and Sailaja Vedantam and Wood, {Andrew R.} and Liming Liang and Valgerdur Steinthorsdottir and Gudmar Thorleifsson and Dermitzakis, {Emmanouil T.} and Dimas, {Antigone S.} and Fredrik Karpe and Min, {Josine L.} and George Nicholson and Clegg, {Deborah J.} and Thomas Person and Krohn, {Jon P.} and Sabrina Bauer and Christa Buechler and Kristina Eisinger and Am{\'e}lie Bonnefond and Philippe Froguel and Hottenga, {Jouke Jan} and Inga Prokopenko and Waite, {Lindsay L.} and Harris, {Tamara B.} and Smith, {Albert Vernon} and Shuldiner, {Alan R.} and McArdle, {Wendy L.} and Caulfield, {Mark J.} and Munroe, {Patricia B.} and Henrik Gr{\"o}nberg and Chen, {Yii Der Ida} and Guo Li and Beckmann, {Jacques S.} and Toby Johnson and Unnur Thorsteinsdottir and Maris Teder-Laving and Khaw, {Kay Tee} and Wareham, {Nicholas J.} and Zhao, {Jing Hua} and Najaf Amin and Oostra, {Ben A.} and Kraja, {Aldi T.} and Province, {Michael A.} and Cupples, {L. Adrienne} and Heard-Costa, {Nancy L.} and Jaakko Kaprio and Samuli Ripatti and Ida Surakka and Collins, {Francis S.} and Jouko Saramies and Jaakko Tuomilehto and Antti Jula and Veikko Salomaa and Jeanette Erdmann and Christian Hengstenberg and Christina Loley and Heribert Schunkert and Claudia Lamina and Wichmann, {H. Erich} and Eva Albrecht and Christian Gieger and Hicks, {Andrew A.} and {\AA}sa Johansson and Pramstaller, {Peter P.} and Sekar Kathiresan and Speliotes, {Elizabeth K.} and Brenda Penninx and Hartikainen, {Anna Liisa} and Jarvelin, {Marjo Riitta} and Ulf Gyllensten and Boomsma, {Dorret I.} and Harry Campbell and Wilson, {James F.} and Chanock, {Stephen J.} and Martin Farrall and Anuj Goel and Carolina Medina-Gomez and Fernando Rivadeneira and Karol Estrada and Uitterlinden, {Andr{\'e} G.} and Albert Hofman and Zillikens, {M. Carola} and {den Heijer}, Martin and Kiemeney, {Lambertus A.} and Andrea Maschio and Per Hall and Jonathan Tyrer and Alexander Teumer and Henry V{\"o}lzke and Peter Kovacs and Anke T{\"o}njes and Massimo Mangino and Spector, {Tim D.} and Caroline Hayward and Igor Rudan and Hall, {Alistair S.} and Samani, {Nilesh J.} and Attwood, {Antony Paul} and Sambrook, {Jennifer G.} and Joseph Hung and Palmer, {Lyle J.} and Lokki, {Marja Liisa} and Juha Sinisalo and Gabrielle Boucher and Heikki Huikuri and Mattias Lorentzon and Claes Ohlsson and Niina Eklund and Eriksson, {Johan G.} and Cristina Barlassina and Carlo Rivolta and Nolte, {Ilja M.} and Harold Snieder and {van der Klauw}, {Melanie M.} and {van Vliet-Ostaptchouk}, {Jana V.} and Gejman, {Pablo V.} and Jianxin Shi and Jacobs, {Kevin B.} and Zhaoming Wang and Bakker, {Stephan J L} and {Mateo Leach}, Irene and Gerjan Navis and {van der Harst}, Pim and Martin, {Nicholas G.} and Medland, {Sarah E.} and Montgomery, {Grant W.} and Jian Yang and Chasman, {Daniel I.} and Ridker, {Paul M.} and Rose, {Lynda M.} and Terho Lehtim{\"a}ki and Olli Raitakari and Devin Absher and Carlos Iribarren and Hanneke Basart and Hovingh, {Kees G.} and Elina Hypp{\"o}nen and Chris Power and Denise Anderson and Beilby, {John P.} and Jennie Hui and Jennifer Jolley and Hendrik Sager and Bornstein, {Stefan R.} and Schwarz, {Peter E H} and Kati Kristiansson and Markus Perola and Jaana Lindstr{\"o}m and Swift, {Amy J.} and Matti Uusitupa and Mustafa Atalay and Lakka, {Timo A.} and Rainer Rauramaa and Bolton, {Jennifer L.} and Gerry Fowkes and Fraser, {Ross M.} and Price, {Jackie F.} and Krista Fischer and Kaarel Krjut{\AA}kov and Andres Metspalu and Evelin Mihailov and Claudia Langenberg and Jian'an Luan and Ong, {Ken K.} and Chines, {Peter S.} and Keinanen-Kiukaanniemi, {Sirkka M.} and Saaristo, {Timo E.} and Sarah Edkins and Franks, {Paul W.} and G{\"o}ran Hallmans and Dmitry Shungin and {da Morris}, Andrewvid and Palmer, {Colin N A} and Raimund Erbel and Susanne Moebus and N{\"o}then, {Markus M.} and Sonali Pechlivanis and Kristian Hveem and Narisu Narisu and Anders Hamsten and Humphries, {Steve E.} and Strawbridge, {Rona J.} and Elena Tremoli and Harald Grallert and Barbara Thorand and Thomas Illig and Wolfgang Koenig and Martina M{\"u}ller-Nurasyid and Annette Peters and Boehm, {Bernhard O.} and Kleber, {Marcus E.} and Winfried M{\"a}rz and Winkelmann, {Bernhard R.} and Johanna Kuusisto and Markku Laakso and Dominique Arveiler and Giancarlo Cesana and Kari Kuulasmaa and Jarmo Virtamo and Yarnell, {John W G} and Diana Kuh and Andrew Wong and Lars Lind and {de Faire}, Ulf and Bruna Gigante and Magnusson, {Patrik K E} and Pedersen, {Nancy L.} and George Dedoussis and Maria Dimitriou and Genovefa Kolovou and Stavroula Kanoni and Kathleen Stirrups and Bonnycastle, {Lori L.} and Inger Nj{\o}lstad and Tom Wilsgaard and Andrea Ganna and Emil Rehnberg and Aroon Hingorani and Mika Kivimaki and Meena Kumari and Assimes, {Themistocles L.} and In{\^e}s Barroso and Michael Boehnke and Borecki, {Ingrid B.} and Panos Deloukas and Fox, {Caroline S.} and Timothy Frayling and Groop, {Leif C.} and Talin Haritunians and David Hunter and Erik Ingelsson and Kaplan, {Robert C.} and Mohlke, {Karen L.} and O'Connell, {Jeffrey R.} and David Schlessinger and Strachan, {David P.} and Kari Stefansson and {van Duijn}, {Cornelia M.} and Abecasis, {Gon{\cc}alo R.} and McCarthy, {Mark I.} and Hirschhorn, {Joel N.} and Lu Qi and Loos, {Ruth J F} and Lindgren, {Cecilia M.} and North, {Kari E.} and Heid, {Iris M.}",
year = "2013",
month = "6",
doi = "10.1371/journal.pgen.1003500",
language = "English (US)",
volume = "9",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

AU - Randall, Joshua C.

AU - Winkler, Thomas W.

AU - Kutalik, Zoltán

AU - Berndt, Sonja I.

AU - Jackson, Anne U.

AU - Monda, Keri L.

AU - Kilpeläinen, Tuomas O.

AU - Esko, Tõnu

AU - Mägi, Reedik

AU - Li, Shengxu

AU - Workalemahu, Tsegaselassie

AU - Feitosa, Mary F.

AU - Croteau-Chonka, Damien C.

AU - Day, Felix R.

AU - Fall, Tove

AU - Ferreira, Teresa

AU - Gustafsson, Stefan

AU - Locke, Adam E.

AU - Mathieson, Iain

AU - Scherag, Andre

AU - Vedantam, Sailaja

AU - Wood, Andrew R.

AU - Liang, Liming

AU - Steinthorsdottir, Valgerdur

AU - Thorleifsson, Gudmar

AU - Dermitzakis, Emmanouil T.

AU - Dimas, Antigone S.

AU - Karpe, Fredrik

AU - Min, Josine L.

AU - Nicholson, George

AU - Clegg, Deborah J.

AU - Person, Thomas

AU - Krohn, Jon P.

AU - Bauer, Sabrina

AU - Buechler, Christa

AU - Eisinger, Kristina

AU - Bonnefond, Amélie

AU - Froguel, Philippe

AU - Hottenga, Jouke Jan

AU - Prokopenko, Inga

AU - Waite, Lindsay L.

AU - Harris, Tamara B.

AU - Smith, Albert Vernon

AU - Shuldiner, Alan R.

AU - McArdle, Wendy L.

AU - Caulfield, Mark J.

AU - Munroe, Patricia B.

AU - Grönberg, Henrik

AU - Chen, Yii Der Ida

AU - Li, Guo

AU - Beckmann, Jacques S.

AU - Johnson, Toby

AU - Thorsteinsdottir, Unnur

AU - Teder-Laving, Maris

AU - Khaw, Kay Tee

AU - Wareham, Nicholas J.

AU - Zhao, Jing Hua

AU - Amin, Najaf

AU - Oostra, Ben A.

AU - Kraja, Aldi T.

AU - Province, Michael A.

AU - Cupples, L. Adrienne

AU - Heard-Costa, Nancy L.

AU - Kaprio, Jaakko

AU - Ripatti, Samuli

AU - Surakka, Ida

AU - Collins, Francis S.

AU - Saramies, Jouko

AU - Tuomilehto, Jaakko

AU - Jula, Antti

AU - Salomaa, Veikko

AU - Erdmann, Jeanette

AU - Hengstenberg, Christian

AU - Loley, Christina

AU - Schunkert, Heribert

AU - Lamina, Claudia

AU - Wichmann, H. Erich

AU - Albrecht, Eva

AU - Gieger, Christian

AU - Hicks, Andrew A.

AU - Johansson, Åsa

AU - Pramstaller, Peter P.

AU - Kathiresan, Sekar

AU - Speliotes, Elizabeth K.

AU - Penninx, Brenda

AU - Hartikainen, Anna Liisa

AU - Jarvelin, Marjo Riitta

AU - Gyllensten, Ulf

AU - Boomsma, Dorret I.

AU - Campbell, Harry

AU - Wilson, James F.

AU - Chanock, Stephen J.

AU - Farrall, Martin

AU - Goel, Anuj

AU - Medina-Gomez, Carolina

AU - Rivadeneira, Fernando

AU - Estrada, Karol

AU - Uitterlinden, André G.

AU - Hofman, Albert

AU - Zillikens, M. Carola

AU - den Heijer, Martin

AU - Kiemeney, Lambertus A.

AU - Maschio, Andrea

AU - Hall, Per

AU - Tyrer, Jonathan

AU - Teumer, Alexander

AU - Völzke, Henry

AU - Kovacs, Peter

AU - Tönjes, Anke

AU - Mangino, Massimo

AU - Spector, Tim D.

AU - Hayward, Caroline

AU - Rudan, Igor

AU - Hall, Alistair S.

AU - Samani, Nilesh J.

AU - Attwood, Antony Paul

AU - Sambrook, Jennifer G.

AU - Hung, Joseph

AU - Palmer, Lyle J.

AU - Lokki, Marja Liisa

AU - Sinisalo, Juha

AU - Boucher, Gabrielle

AU - Huikuri, Heikki

AU - Lorentzon, Mattias

AU - Ohlsson, Claes

AU - Eklund, Niina

AU - Eriksson, Johan G.

AU - Barlassina, Cristina

AU - Rivolta, Carlo

AU - Nolte, Ilja M.

AU - Snieder, Harold

AU - van der Klauw, Melanie M.

AU - van Vliet-Ostaptchouk, Jana V.

AU - Gejman, Pablo V.

AU - Shi, Jianxin

AU - Jacobs, Kevin B.

AU - Wang, Zhaoming

AU - Bakker, Stephan J L

AU - Mateo Leach, Irene

AU - Navis, Gerjan

AU - van der Harst, Pim

AU - Martin, Nicholas G.

AU - Medland, Sarah E.

AU - Montgomery, Grant W.

AU - Yang, Jian

AU - Chasman, Daniel I.

AU - Ridker, Paul M.

AU - Rose, Lynda M.

AU - Lehtimäki, Terho

AU - Raitakari, Olli

AU - Absher, Devin

AU - Iribarren, Carlos

AU - Basart, Hanneke

AU - Hovingh, Kees G.

AU - Hyppönen, Elina

AU - Power, Chris

AU - Anderson, Denise

AU - Beilby, John P.

AU - Hui, Jennie

AU - Jolley, Jennifer

AU - Sager, Hendrik

AU - Bornstein, Stefan R.

AU - Schwarz, Peter E H

AU - Kristiansson, Kati

AU - Perola, Markus

AU - Lindström, Jaana

AU - Swift, Amy J.

AU - Uusitupa, Matti

AU - Atalay, Mustafa

AU - Lakka, Timo A.

AU - Rauramaa, Rainer

AU - Bolton, Jennifer L.

AU - Fowkes, Gerry

AU - Fraser, Ross M.

AU - Price, Jackie F.

AU - Fischer, Krista

AU - KrjutÅkov, Kaarel

AU - Metspalu, Andres

AU - Mihailov, Evelin

AU - Langenberg, Claudia

AU - Luan, Jian'an

AU - Ong, Ken K.

AU - Chines, Peter S.

AU - Keinanen-Kiukaanniemi, Sirkka M.

AU - Saaristo, Timo E.

AU - Edkins, Sarah

AU - Franks, Paul W.

AU - Hallmans, Göran

AU - Shungin, Dmitry

AU - da Morris, Andrewvid

AU - Palmer, Colin N A

AU - Erbel, Raimund

AU - Moebus, Susanne

AU - Nöthen, Markus M.

AU - Pechlivanis, Sonali

AU - Hveem, Kristian

AU - Narisu, Narisu

AU - Hamsten, Anders

AU - Humphries, Steve E.

AU - Strawbridge, Rona J.

AU - Tremoli, Elena

AU - Grallert, Harald

AU - Thorand, Barbara

AU - Illig, Thomas

AU - Koenig, Wolfgang

AU - Müller-Nurasyid, Martina

AU - Peters, Annette

AU - Boehm, Bernhard O.

AU - Kleber, Marcus E.

AU - März, Winfried

AU - Winkelmann, Bernhard R.

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Arveiler, Dominique

AU - Cesana, Giancarlo

AU - Kuulasmaa, Kari

AU - Virtamo, Jarmo

AU - Yarnell, John W G

AU - Kuh, Diana

AU - Wong, Andrew

AU - Lind, Lars

AU - de Faire, Ulf

AU - Gigante, Bruna

AU - Magnusson, Patrik K E

AU - Pedersen, Nancy L.

AU - Dedoussis, George

AU - Dimitriou, Maria

AU - Kolovou, Genovefa

AU - Kanoni, Stavroula

AU - Stirrups, Kathleen

AU - Bonnycastle, Lori L.

AU - Njølstad, Inger

AU - Wilsgaard, Tom

AU - Ganna, Andrea

AU - Rehnberg, Emil

AU - Hingorani, Aroon

AU - Kivimaki, Mika

AU - Kumari, Meena

AU - Assimes, Themistocles L.

AU - Barroso, Inês

AU - Boehnke, Michael

AU - Borecki, Ingrid B.

AU - Deloukas, Panos

AU - Fox, Caroline S.

AU - Frayling, Timothy

AU - Groop, Leif C.

AU - Haritunians, Talin

AU - Hunter, David

AU - Ingelsson, Erik

AU - Kaplan, Robert C.

AU - Mohlke, Karen L.

AU - O'Connell, Jeffrey R.

AU - Schlessinger, David

AU - Strachan, David P.

AU - Stefansson, Kari

AU - van Duijn, Cornelia M.

AU - Abecasis, Gonçalo R.

AU - McCarthy, Mark I.

AU - Hirschhorn, Joel N.

AU - Qi, Lu

AU - Loos, Ruth J F

AU - Lindgren, Cecilia M.

AU - North, Kari E.

AU - Heid, Iris M.

PY - 2013/6

Y1 - 2013/6

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.

UR - http://www.scopus.com/inward/record.url?scp=84879677633&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879677633&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1003500

DO - 10.1371/journal.pgen.1003500

M3 - Article

VL - 9

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 6

M1 - e1003500

ER -