학술논문
Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits
Document Type
Author
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, Asa; 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; Krjutå Kov, 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; Morris, Andrew David; 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; 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
Source
PLOS Genetics. 9(6):e1003500
Subject
Language
English
ISSN
1553-7390
1553-7404
1553-7404
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.