Genetic studies of body mass index yield new insights for obesity biology

Locke, A. E. et al. (2015) Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), pp. 197-206. (doi: 10.1038/nature14177) (PMID:25673413) (PMCID:PMC4382211)

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Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Johnson, Dr Paul and Ford, Professor Ian and Dominiczak, Professor Anna and Sattar, Professor Naveed and Strawbridge, Dr Rona
Authors: Locke, A. E., Kahali, B., Berndt, S. I., Justice, A. E., Pers, T. H., Day, F. R., Powell, C., Vedantam, S., Buchkovich, M. L., Yang, J., Croteau-Chonka, D. C., Esko, T., Fall, T., Ferreira, T., Gustafsson, S., Kutalik, Z., Luan, J.’a., Mägi, R., Randall, J. C., Winkler, T. W., Wood, A. R., Workalemahu, T., Faul, J. D., Smith, J. A., Hua Zhao, J., Zhao, W., Chen, J., Fehrmann, R., Hedman, Å. K., Karjalainen, J., Schmidt, E. M., Absher, D., Amin, N., Anderson, D., Beekman, M., Bolton, J. L., Bragg-Gresham, J. L., Buyske, S., Demirkan, A., Deng, G., Ehret, G. B., Feenstra, B., Feitosa, M. F., Fischer, K., Goel, A., Gong, J., Jackson, A. U., Kanoni, S., Kleber, M. E., Kristiansson, K., Lim, U., Lotay, V., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Medland, S. E., Nalls, M. A., Palmer, C. D., Pasko, D., Pechlivanis, S., Peters, M. J., Prokopenko, I., Shungin, D., Stančáková, A., Strawbridge, R. J., Ju Sung, Y., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S. W., van Setten, J., Van Vliet-Ostaptchouk, J. V., Wang, Z., Yengo, L., Zhang, W., Isaacs, A., Albrecht, E., Ärnlöv, J., Arscott, G. M., Attwood, A. P., Bandinelli, S., Barrett, A., Bas, I. N., Bellis, C., Bennett, A. J., Berne, C., Blagieva, R., Blüher, M., Böhringer, S., Bonnycastle, L. L., Böttcher, Y., Boyd, H. A., Bruinenberg, M., Caspersen, I. H., Ida Chen, Y.-D., Clarke, R., Warwick Daw, E., de Craen, A. J. M., Delgado, G., Dimitriou, M., Doney, A. S. F., Eklund, N., Estrada, K., Eury, E., Folkersen, L., Fraser, R. M., Garcia, M. E., Geller, F., Giedraitis, V., Gigante, B., Go, A. S., Golay, A., Goodall, A. H., Gordon, S. D., Gorski, M., Grabe, H.-J., Grallert, H., Grammer, T. B., Gräßler, J., Grönberg, H., Groves, C. J., Gusto, G., Haessler, J., Hall, P., Haller, T., Hallmans, G., Hartman, C. A., Hassinen, M., Hayward, C., Heard-Costa, N. L., Helmer, Q., Hengstenberg, C., Holmen, O., Hottenga, J.-J., James, A. L., Jeff, J. M., Johansson, Å., Jolley, J., Juliusdottir, T., Kinnunen, L., Koenig, W., Koskenvuo, M., Kratzer, W., Laitinen, J., Lamina, C., Leander, K., Lee, N. R., Lichtner, P., Lind, L., Lindström, J., Sin Lo, K., Lobbens, S., Lorbeer, R., Lu, Y., Mach, F., Magnusson, P. K. E., Mahajan, A., McArdle, W. L., McLachlan, S., Menni, C., Merger, S., Mihailov, E., Milani, L., Moayyeri, A., Monda, K. L., Morken, M. A., Mulas, A., Müller, G., Müller-Nurasyid, M., Musk, A. W., Nagaraja, R., Nöthen, M. M., Nolte, I. M., Pilz, S., Rayner, N. W., Renstrom, F., Rettig, R., Ried, J. S., Ripke, S., Robertson, N. R., Rose, L. M., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F. R., Scott, W. R., Seufferlein, T., Shi, J., Vernon Smith, A., Smolonska, J., Stanton, A. V., Steinthorsdottir, V., Stirrups, K., Stringham, H. M., Sundström, J., Swertz, M. A., Swift, A. J., Syvänen, A.-C., Tan, S.-T., Tayo, B. O., Thorand, B., Thorleifsson, G., Tyrer, J. P., Uh, H.-W., Vandenput, L., Verhulst, F. C., Vermeulen, S. H., Verweij, N., Vonk, J. M., Waite, L. L., Warren, H. R., Waterworth, D., Weedon, M. N., Wilkens, L. R., Willenborg, C., Wilsgaard, T., Wojczynski, M. K., Wong, A., Wright, A. F., Zhang, Q., Brennan, E. P., Choi, M., Dastani, Z., Drong, A. W., Eriksson, P., Franco-Cereceda, A., Gådin, J. R., Gharavi, A. G., Goddard, M. E., Handsaker, R. E., Huang, J., Karpe, F., Kathiresan, S., Keildson, S., Kiryluk, K., Kubo, M., Lee, J.-Y., Liang, L., Lifton, R. P., Ma, B., McCarroll, S. A., McKnight, A. J., Min, J. L., Moffatt, M. F., Montgomery, G. W., Murabito, J. M., Nicholson, G., Nyholt, D. R., Okada, Y., Perry, J. R. B., Dorajoo, R., Reinmaa, E., Salem, R. M., Sandholm, N., Scott, R. A., Stolk, L., Takahashi, A., Tanaka, T., van’t Hooft, F. M., Vinkhuyzen, A. A. E., Westra, H.-J., Zheng, W., Zondervan, K. T., Heath, A. C., Arveiler, D., Bakker, S. J. L., Beilby, J., Bergman, R. N., Blangero, J., Bovet, P., Campbell, H., Caulfield, M. J., Cesana, G., Chakravarti, A., Chasman, D. I., Chines, P. S., Collins, F. S., Crawford, D. C., Adrienne Cupples, L., Cusi, D., Danesh, J., de Faire, U., den Ruijter, H. M., Dominiczak, A. F., Erbel, R., Erdmann, J., Eriksson, J. G., Farrall, M., Felix, S. B., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, N. G., Forrester, T., Franco, O. H., Gansevoort, R. T., Gejman, P. V., Gieger, C., Gottesman, O., Gudnason, V., Gyllensten, U., Hall, A. S., Harris, T. B., Hattersley, A. T., Hicks, A. A., Hindorff, L. A., Hingorani, A. D., Hofman, A., Homuth, G., Kees Hovingh, G., Humphries, S. E., Hunt, S. C., Hyppönen, E., Illig, T., Jacobs, K. B., Jarvelin, M.-R., Jöckel, K.-H., Johansen, B., Jousilahti, P., Wouter Jukema, J., Jula, A. M., Kaprio, J., Kastelein, J. J. P., Keinanen-Kiukaanniemi, S. M., Kiemeney, L. A., Knekt, P., Kooner, J. S., Kooperberg, C., Kovacs, P., Kraja, A. T., Kumari, M., Kuusisto, J., Lakka, T. A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lyssenko, V., Männistö, S., Marette, A., Matise, T. C., McKenzie, C. A., McKnight, B., Moll, F. L., Morris, A. D., Morris, A. P., Murray, J. C., Nelis, M., Ohlsson, C., Oldehinkel, A. J., Ong, K. K., Madden, P. A. F., Pasterkamp, G., Peden, J. F., Peters, A., Postma, D. S., Pramstaller, P. P., Price, J. F., Qi, L., Raitakari, O. T., Rankinen, T., Rao, D. C., Rice, T. K., Ridker, P. M., Rioux, J. D., Ritchie, M. D., Rudan, I., Salomaa, V., Samani, N. J., Saramies, J., Sarzynski, M. A., Schunkert, H., Schwarz, P. E. H., Sever, P., Shuldiner, A. R., Sinisalo, J., Stolk, R. P., Strauch, K., Tönjes, A., Trégouët, D.-A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, M.-C., Völker, U., Waeber, G., Willemsen, G., Witteman, J. C., Carola Zillikens, M., Adair, L. S., Amouyel, P., Asselbergs, F. W., Assimes, T. L., Bochud, M., Boehm, B. O., Boerwinkle, E., Bornstein, S. R., Bottinger, E. P., Bouchard, C., Cauchi, S., Chambers, J. C., Chanock, S. J., Cooper, R. S., de Bakker, P. I. W., Dedoussis, G., Ferrucci, L., Franks, P. W., Froguel, P., Groop, L. C., Haiman, C. A., Hamsten, A., Hui, J., Hunter, D. J., Hveem, K., Kaplan, R. C., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, N. G., März, W., Melbye, M., Metspalu, A., Moebus, S., Munroe, P. B., Njølstad, I., Oostra, B. A., Palmer, C. N. A., Pedersen, N. L., Perola, M., Pérusse, L., Peters, U., Power, C., Quertermous, T., Rauramaa, R., Rivadeneira, F., Saaristo, T. E., Saleheen, D., Sattar, N., Schadt, E. E., Schlessinger, D., Eline Slagboom, P., Snieder, H., Spector, T. D., Thorsteinsdottir, U., Stumvoll, M., Tuomilehto, J., Uitterlinden, A. G., Uusitupa, M., van der Harst, P., Walker, M., Wallaschofski, H., Wareham, N. J., Watkins, H., Weir, D. R., Wichmann, H.-E., Wilson, J. F., Zanen, P., Borecki, I. B., Deloukas, P., Fox, C. S., Heid, I. M., O’Connell, J. R., Strachan, D. P., Stefansson, K., van Duijn, C. M., Abecasis, G. R., Franke, L., Frayling, T. M., McCarthy, M. I., Visscher, P. M., Scherag, A., Willer, C. J., Boehnke, M., Mohlke, K. L., Lindgren, C. M., Beckmann, J. S., Barroso, I., North, K. E., Ingelsson, E., Hirschhorn, J. N., Loos, R. J. F., Speliotes, E. K., and MAGIC Investigators,
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Nature
Publisher:Nature Publishing Group
ISSN:0028-0836
ISSN (Online):1476-4687

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