Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Scott, R.A. et al. (2013) Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nature Genetics, 44(9), pp. 991-1005. (doi: 10.1038/ng.2385)

Abstract

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Johnson, Dr Paul and Ford, Professor Ian and Sattar, Professor Naveed and Strawbridge, Dr Rona
• Authors: Scott, R.A., Lagou, V., Welch, R.P., Wheeler, E., Montasser, M.E., Luan, J., Mägi, R., Strawbridge, R.J., Rehnberg, E., Gustafsson, S., Kanoni, S., Rasmussen-Torvik, L.J., Yengo, L., Lecoeur, C., Shungin, D., Sanna, S., Sidore, C., Johnson, P.C.D., Jukema, J.W., Johnson, T., Mahajan, A., Verweij, N., Thorleifsson, G., Hottenga, J.-J., Shah, S., Smith, A.V., Sennblad, B., Gieger, C., Salo, P., Perola, M., Timpson, N.J., Evans, D.M., Pourcain, B.S., Wu, Y., Andrews, J.S., Hui, J., Bielak, L.F., Zhao, W., Horikoshi, M., Navarro, P., Isaacs, A., O'Connell, J.R., Stirrups, K., Vitart, V., Hayward, C., Esko, T., Mihailov, E., Fraser, R.M., Fall, T., Voight, B.F., Raychaudhuri, S., Chen, H., Lindgren, C.M., Morris, A.P., Rayner, N.W., Robertson, N., Rybin, D., Liu, C.-T., Beckmann, J.S., Willems, S.M., Chines, P.S., Jackson, A.U., Kang, H.M., Stringham, H.M., Song, K., Tanaka, T., Peden, J.F., Goel, A., Hicks, A.A., An, P., Müller-Nurasyid, M., Franco-Cereceda, A., Folkersen, L., Marullo, L., Jansen, H., Oldehinkel, A.J., Bruinenberg, M., Pankow, J.S., North, K.E., Forouhi, N.G., Loos, R.J.F., Edkins, S., Varga, T.V., Hallmans, G., Oksa, H., Antonella, M., Nagaraja, R., Trompet, S., Ford, I., Bakker, S.J.L., Kong, A., Kumari, M., Gigante, B., Herder, C., Munroe, P.B., Caulfield, M., Antti, J., Mangino, M., Small, K., Miljkovic, I., Liu, Y., Atalay, M., Kiess, W., James, A.L., Rivadeneira, F., Uitterlinden, A.G., Palmer, C.N.A., Doney, A.S.F., Willemsen, G., Smit, J.H., Campbell, S., Polasek, O., Bonnycastle, L.L., Hercberg, S., Dimitriou, M., Bolton, J.L., Fowkes, G.R., Kovacs, P., Lindström, J., Zemunik, T., Bandinelli, S., Wild, S.H., Basart, H.V., Rathmann, W., Grallert, H., Maerz, W., Kleber, M.E., Boehm, B.O., Peters, A., Pramstaller, P.P., Province, M.A., Borecki, I.B., Hastie, N.D., Rudan, I., Campbell, H., Watkins, H., Farrall, M., Stumvoll, M., Ferrucci, L., Waterworth, D.M., Bergman, R.N., Collins, F.S., Tuomilehto, J., Watanabe, R.M., de Geus, E.J.C., Penninx, B.W., Hofman, A., Oostra, B.A., Psaty, B.M., Vollenweider, P., Wilson, J.F., Wright, A.F., Hovingh, G.K., Metspalu, A., Uusitupa, M., Magnusson, P.K.E., Kyvik, K.O., Kaprio, J., Price, J.F., Dedoussis, G.V., Deloukas, P., Meneton, P., Lind, L., Boehnke, M., Shuldiner, A.R., van Duijn, C.M., Morris, A.D., Toenjes, A., Peyser, P.A., Beilby, J.P., Körner, A., Kuusisto, J., Laakso, M., Bornstein, S.R., Schwarz, P.E.H., Lakka, T.A., Rauramaa, R., Adair, L.S., Smith, G.D., Spector, T.D., Illig, T., de Faire, U., Hamsten, A., Gudnason, V., Kivimaki, M., Hingorani, A., Keinanen-Kiukaanniemi, S.M., Saaristo, T.E., Boomsma, D.I., Stefansson, K., van der Harst, P., Dupuis, J., Pedersen, N.L., Sattar, N., Harris, T.B., Cucca, F., Ripatti, S., Salomaa, V., Mohlke, K.L., Balkau, B., Froguel, P., Pouta, A., Jarvelin, M.-R., Wareham, N.J., Bouatia-Naji, N., McCarthy, M.I., Franks, P.W., Meigs, J.B., Teslovich, T.M., Florez, J.C., Langenberg, C., Ingelsson, E., Prokopenko, I., and Barroso, I.
• 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 > Robertson Centre; 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
• Published Online: 12 August 2012