| Autor: |
Mahajan, A. Taliun, D. Thurner, M. Robertson, N.R. Torres, J.M. Rayner, N.W. Payne, A.J. Steinthorsdottir, V. Scott, R.A. Grarup, N. Cook, J.P. Schmidt, E.M. Wuttke, M. Sarnowski, C. Mägi, R. Nano, J. Gieger, C. Trompet, S. Lecoeur, C. Preuss, M.H. Prins, B.P. Guo, X. Bielak, L.F. Below, J.E. Bowden, D.W. Chambers, J.C. Kim, Y.J. Ng, M.C.Y. Petty, L.E. Sim, X. Zhang, W. Bennett, A.J. Bork-Jensen, J. Brummett, C.M. Canouil, M. Ec kardt, K.-U. Fischer, K. Kardia, S.L.R. Kronenberg, F. Läll, K. Liu, C.-T. Locke, A.E. Luan, J. Ntalla, I. Nylander, V. Schönherr, S. Schurmann, C. Yengo, L. Bottinger, E.P. Brandslund, I. Christensen, C. Dedoussis, G. Florez, J.C. Ford, I. Franco, O.H. Frayling, T.M. Giedraitis, V. Hackinger, S. Hattersley, A.T. Herder, C. Ikram, M.A. Ingelsson, M. Jørgensen, M.E. Jørgensen, T. Kriebel, J. Kuusisto, J. Ligthart, S. Lindgren, C.M. Linneberg, A. Lyssenko, V. Mamakou, V. Meitinger, T. Mohlke, K.L. Morris, A.D. Nadkarni, G. Pankow, J.S. Peters, A. Sattar, N. Stančáková, A. Strauch, K. Taylor, K.D. Thorand, B. Thorleifsson, G. Thorsteinsdottir, U. Tuomilehto, J. Witte, D.R. Dupuis, J. Peyser, P.A. Zeggini, E. Loos, R.J.F. Froguel, P. Ingelsson, E. Lind, L. Groop, L. Laakso, M. Collins, F.S. Jukema, J.W. Palmer, C.N.A. Grallert, H. Metspalu, A. Dehghan, A. Köttgen, A. Abecasis, G.R. Meigs, J.B. Rotter, J.I. Marchini, J. Pedersen, O. Hansen, T. Langenberg, C. Wareham, N.J. Stefansson, K. Gloyn, A.L. Morris, A.P. Boehnke, M. McCarthy, M.I. |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Popis: |
We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence). © 2018, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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