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

Heid, I. M. et al. (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. (doi: 10.1038/ng.685) (PMID:20935629) (PMCID:PMC3000924)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Strawbridge, Dr Rona
• Authors: Heid, I. M., Jackson, A. U., Randall, J. C., Winkler, T. W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M. C., Speliotes, E. K., Mägi, R., Workalemahu, T., White, C. C., Bouatia-Naji, N., Harris, T. B., Berndt, S. I., Ingelsson, E., Willer, C. J., Weedon, M. N., Luan, J.'a., Vedantam, S., Esko, T., Kilpeläinen, T. O., Kutalik, Z., Li, S., Monda, K. L., Dixon, A. L., Holmes, C. C., Kaplan, L. M., Liang, L., Min, J. L., Moffatt, M. F., Molony, C., Nicholson, G., Schadt, E. E., Zondervan, K. T., Feitosa, M. F., Ferreira, T., Allen, H. L., Weyant, R. J., Wheeler, E., Wood, A. R., Estrada, K., Goddard, M. E., Lettre, G., Mangino, M., Nyholt, D. R., Purcell, S., Smith, A. V., Visscher, P. M., Yang, J., McCarroll, S. A., Nemesh, J., Voight, B. F., Absher, D., Amin, N., Aspelund, T., Coin, L., Glazer, N. L., Hayward, C., Heard-Costa, N. L., Hottenga, J.-J., Johansson, Å., Johnson, T., Kaakinen, M., Kapur, K., Ketkar, S., Knowles, J. W., Kraft, P., Kraja, A. T., Lamina, C., Leitzmann, M. F., McKnight, B., Morris, A. P., Ong, K. K., Perry, J. R. B., Peters, M. J., Polasek, O., Prokopenko, I., Rayner, N. W., Ripatti, S., Rivadeneira, F., Robertson, N. R., Sanna, S., Sovio, U., Surakka, I., Teumer, A., van Wingerden, S., Vitart, V., Zhao, J. H., Cavalcanti-Proença, C., Chines, P. S., Fisher, E., Kulzer, J. R., Lecoeur, C., Narisu, N., Sandholt, C., Scott, L. J., Silander, K., Stark, K., Tammesoo, M.-L., Teslovich, T. M., Timpson, N. J., Watanabe, R. M., Welch, R., Chasman, D. I., Cooper, M. N., Jansson, J.-O., Kettunen, J., Lawrence, R. W., Pellikka, N., Perola, M., Vandenput, L., Alavere, H., Almgren, P., Atwood, L. D., Bennett, A. J., Biffar, R., Bonnycastle, L. L., Bornstein, S. R., Buchanan, T. A., Campbell, H., Day, I. N. M., Dei, M., Dörr, M., Elliott, P., Erdos, M. R., Eriksson, J. G., Freimer, N. B., Fu, M., Gaget, S., Geus, E. J. C., Gjesing, A. P., Grallert, H., Gräßler, J., Groves, C. J., Guiducci, C., Hartikainen, A.-L., Hassanali, N., Havulinna, A. S., Herzig, K.-H., Hicks, A. A., Hui, J., Igl, W., Jousilahti, P., Jula, A., Kajantie, E., Kinnunen, L., Kolcic, I., Koskinen, S., Kovacs, P., Kroemer, H. K., Krzelj, V., Kuusisto, J., Kvaloy, K., Laitinen, J., Lantieri, O., Lathrop, G. M., Lokki, M.-L., Luben, R. N., Ludwig, B., McArdle, W. L., McCarthy, A., Morken, M. A., Nelis, M., Neville, M. J., Paré, G., Parker, A. N., Peden, J. F., Pichler, I., Pietiläinen, K. H., Platou, C. G. P., Pouta, A., Ridderstråle, M., Samani, N. J., Saramies, J., Sinisalo, J., Smit, J. H., Strawbridge, R. J., Stringham, H. M., Swift, A. J., Teder-Laving, M., Thomson, B., Usala, G., van Meurs, J. B. J., van Ommen, G.-J., Vatin, V., Volpato, C. B., Wallaschofski, H., Walters, G. B., Widen, E., Wild, S. H., Willemsen, G., Witte, D. R., Zgaga, L., Zitting, P., Beilby, J. P., James, A. L., Kähönen, M., Lehtimäki, T., Nieminen, M. S., Ohlsson, C., Palmer, L. J., Raitakari, O., Ridker, P. M., Stumvoll, M., Tönjes, A., Viikari, J., Balkau, B., Ben-Shlomo, Y., Bergman, R. N., Boeing, H., Smith, G. D., Ebrahim, S., Froguel, P., Hansen, T., Hengstenberg, C., Hveem, K., Isomaa, B., Jørgensen, T., Karpe, F., Khaw, K.-T., Laakso, M., Lawlor, D. A., Marre, M., Meitinger, T., Metspalu, A., Midthjell, K., Pedersen, O., Salomaa, V., Schwarz, P. E. H., Tuomi, T., Tuomilehto, J., Valle, T. T., Wareham, N. J., Arnold, A. M., Beckmann, J. S., Bergmann, S., Boerwinkle, E., Boomsma, D. I., Caulfield, M. J., Collins, F. S., Eiriksdottir, G., Gudnason, V., Gyllensten, U., Hamsten, A., Hattersley, A. T., Hofman, A., Hu, F. B., Illig, T., Iribarren, C., Jarvelin, M.-R., Kao, W. H. L., Kaprio, J., Launer, L. J., Munroe, P. B., Oostra, B., Penninx, B. W., Pramstaller, P. P., Psaty, B. M., Quertermous, T., Rissanen, A., Rudan, I., Shuldiner, A. R., Soranzo, N., Spector, T. D., Syvanen, A.-C., Uda, M., Uitterlinden, A., Völzke, H., Vollenweider, P., Wilson, J. F., Witteman, J. C., Wright, A. F., Abecasis, G. R., Boehnke, M., Borecki, I. B., Deloukas, P., Frayling, T. M., Groop, L. C., Haritunians, T., Hunter, D. J., Kaplan, R. C., North, K. E., O'Connell, J. R., Peltonen, L., Schlessinger, D., Strachan, D. P., Hirschhorn, J. N., Assimes, T. L., Wichmann, H.-E., Thorsteinsdottir, U., van Duijn, C. M., Stefansson, K., Cupples, L. A., Loos, R. J. F., Barroso, I., McCarthy, M. I., Fox, C. S., Mohlke, K. L., and Lindgren, C. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 10 October 2010