Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Heid, Iris M., Jackson, Anne U., Randall, Joshua C., Winkler, Thomas W., Qi, Lu, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Zillikens, M. Carola, Speliotes, Elizabeth K., Mägi, Reedik, Workalemahu, Tsegaselassie, White, Charles C., Bouatia-Naji, Nabila, Harris, Tamara B., Berndt, Sonja I., Ingelsson, Erik, Willer, Cristen J., Weedon, Michael N., Luan, Jian'an, Vedantam, Sailaja, Esko, Tõnu, Kilpeläinen, Tuomas O., Kutalik, Zoltán, Li, Shengxu, Monda, Keri L., Dixon, Anna L., Holmes, Christopher C., Kaplan, Lee M., Liang, Liming, Min, Josine L., Moffatt, Miriam F., Molony, Cliona, Nicholson, George, Schadt, Eric E., Zondervan, Krina T., Feitosa, Mary F., Ferreira, Teresa, Allen, Hana Lango, Weyant, Robert J., Wheeler, Eleanor, Wood, Andrew R., Estrada, Karol, Goddard, Michael E., Lettre, Guillaume, Mangino, Massimo, Nyholt, Dale R., Purcell, Shaun, Smith, Albert Vernon, Visscher, Peter M., Yang, Jian, McCarroll, Steven A., Nemesh, James, Voight, Benjamin F, Absher, Devin, Amin, Najaf, Aspelund, Thor, Coin, Lachlan, Glazer, Nicole L, Hayward, Caroline, Heard-Costa, Nancy L, Hottenga, Jouke-Jan, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kapur, Karen, Ketkar, Shamika, Knowles, Joshua W, Kraft, Peter, Kraja, Aldi T, Lamina, Claudia, Leitzmann, Michael F, McKnight, Barbara, Morris, Andrew P, Ong, Ken K, Perry, John R B, Peters, Marjolein J, Polasek, Ozren, Prokopenko, Inga, Rayner, Nigel W, Ripatti, Samuli, Rivadeneira, Fernando, Robertson, Neil R, Sanna, Serena, Sovio, Ulla, Surakka, Ida, Teumer, Alexander, van Wingerden, Sophie, Vitart, Veronique, Zhao, Jing Hua, Cavalcanti-Proença, Christine, Chines, Peter S, Fisher, Eva, Kulzer, Jennifer R, Lecoeur, Cecile, Narisu, Narisu, Sandholt, Camilla, Scott, Laura J, Silander, Kaisa, Stark, Klaus, Tammesoo, Mari-Liis, Teslovich, Tanya M, Timpson, Nicholas John, Watanabe, Richard M, Welch, Ryan, Chasman, Daniel I, Cooper, Matthew N, Jansson, John-Olov, Kettunen, Johannes, Lawrence, Robert W, Pellikka, Niina, Perola, Markus, Vandenput, Liesbeth, Alavere, Helene, Almgren, Peter, Atwood, Larry D, Bennett, Amanda J, Biffar, Reiner, Bonnycastle, Lori L, Bornstein, Stefan R, Buchanan, Thomas A, Campbell, Harry, Day, Ian N M, Dei, Mariano, Dörr, Marcus, Elliott, Paul, Erdos, Michael R, Eriksson, Johan G, Freimer, Nelson B, Fu, Mao, Gaget, Stefan, Geus, Eco J C, Gjesing, Anette P, Grallert, Harald, Gräßler, Jürgen, Groves, Christopher J, Guiducci, Candace, Hartikainen, Anna-Liisa, Hassanali, Neelam, Havulinna, Aki S, Herzig, Karl-Heinz, Hicks, Andrew A, Hui, Jennie, Igl, Wilmar, Jousilahti, Pekka, Jula, Antti, Kajantie, Eero, Kinnunen, Leena, Kolcic, Ivana, Koskinen, Seppo, Kovacs, Peter, Kroemer, Heyo K, Krzelj, Vjekoslav, Kuusisto, Johanna, Kvaloy, Kirsti, Laitinen, Jaana, Lantieri, Olivier, Lathrop, G Mark, Lokki, Marja-Liisa, Luben, Robert N, Ludwig, Barbara, McArdle, Wendy L, McCarthy, Anne, Morken, Mario A, Nelis, Mari, Neville, Matt J, Paré, Guillaume, Parker, Alex N, Peden, John F, Pichler, Irene, Pietiläinen, Kirsi H, Platou, Carl G P, Pouta, Anneli, Ridderstråle, Martin, Samani, Nilesh J, Saramies, Jouko, Sinisalo, Juha, Smit, 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Wareham, Nicholas J, Arnold, Alice M, Beckmann, Jacques S, Bergmann, Sven, Boerwinkle, Eric, Boomsma, Dorret I, Caulfield, Mark J, Collins, Francis S, Eiriksdottir, Gudny, Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Hattersley, Andrew T, Hofman, Albert, Hu, Frank B, Illig, Thomas, Iribarren, Carlos, Jarvelin, Marjo-Riitta, Kao, W H Linda, Kaprio, Jaakko, Launer, Lenore J, Munroe, Patricia B, Oostra, Ben, Penninx, Brenda W, Pramstaller, Peter P, Psaty, Bruce M, Quertermous, Thomas, Rissanen, Aila, Rudan, Igor, Shuldiner, Alan R, Soranzo, Nicole, Spector, Timothy D, Syvanen, Ann-Christine, Uda, Manuela, Uitterlinden, André, Völzke, Henry, Vollenweider, Peter, Wilson, James F, Witteman, Jacqueline C, Wright, Alan F, Abecasis, Gonçalo R, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Frayling, Timothy M, Groop, Leif C, Haritunians, Talin, Hunter, David J, Kaplan, Robert C, North, Kari E, O'Connell, Jeffrey R, Peltonen, Leena, Schlessinger, David, Strachan, David P, Hirschhorn, Joel N, Assimes, Themistocles L, Wichmann, H-Erich, Thorsteinsdottir, Unnur, van Duijn, Cornelia M, Stefansson, Kari, Cupples, L. Adrienne, Loos, Ruth J. F., Barroso, Inês, McCarthy, Mark I., Fox, Caroline S., Mohlke, Karen L., & Lindgren, Cecilia M. (2010) Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nature Genetics, 42(11), pp. 949-960.

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Abstract

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

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ID Code: 92024
Item Type: Journal Article
Refereed: Yes
DOI: 10.1038/ng.685
ISSN: 1546-1718
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 18 Jan 2016 22:46
Last Modified: 14 Feb 2016 23:14

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