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Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
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 Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility..pdf | Accepted version | 647.39 kB | Adobe PDF | View/Open |
| Title: | Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility |
| Authors: | Mahajan, A Go, MJ Zhang, W Below, JE Gaulton, KJ Ferreira, T Horikoshi, M Johnson, AD Ng, MCY Prokopenko, I Saleheen, D Wang, X Zeggini, E Abecasis, GR Adair, LS Almgren, P Atalay, M Aung, T Baldassarre, D Balkau, B Bao, Y Barnett, AH Barroso, I Basit, A Been, LF Beilby, J Bell, GI Benediktsson, R Bergman, RN Boehm, BO Boerwinkle, E Bonnycastle, LL Burtt, N Cai, Q Campbell, H Carey, J Cauchi, S Caulfield, M Chan, JCN Chang, L-C Chang, T-J Chang, Y-C Charpentier, G Chen, C-H Chen, H Chen, Y-T Chia, K-S Chidambaram, M Chines, PS Cho, NH Cho, YM Chuang, L-M Collins, FS Cornelis, MC Couper, DJ Crenshaw, AT Van Dam, RM Danesh, J Das, D De Faire, U Dedoussis, G Deloukas, P Dimas, AS Dina, C Doney, ASF Donnelly, PJ Dorkhan, M Van Duijn, C Dupuis, J Edkins, S Elliott, P Emilsson, V Erbel, R Eriksson, JG Escobedo, J Esko, T Eury, E Florez, JC Fontanillas, P Forouhi, NG Forsen, T Fox, C Fraser, RM Frayling, TM Froguel, P Frossard, P Gao, Y Gertow, K Gieger, C Gigante, B Grallert, H Grant, GB Groop, LC Groves, CJ Grundberg, E Guiducci, C Hamsten, A Han, B-G Hara, K Hassanali, N Hattersley, AT Hayward, C Hedman, AK Herder, C Hofman, A Holmen, OL Hovingh, K Hreidarsson, AB Hu, C Hu, FB Hui, J Humphries, SE Hunt, SE Hunter, DJ Hveem, K Hydrie, ZI Ikegami, H Illig, T Ingelsson, E Islam, M Isomaa, B Jackson, AU Jafar, T James, A Jia, W Joeckel, K-H Jonsson, A Jowett, JBM Kadowaki, T Kang, HM Kanoni, S Kao, WHL Kathiresan, S Kato, N Katulanda, P Keinanen-Kiukaanniemi, SM Kelly, AM Khan, H Khaw, K-T Khor, C-C Kim, H-L Kim, S Kim, YJ Kinnunen, L Klopp, N Kong, A Korpi-Hyovalti, E Kowlessur, S Kraft, P Kravic, J Kristensen, MM Krithika, S Kumar, A Kumate, J Kuusisto, J Kwak, SH Laakso, M Lagou, V Lakka, TA Langenberg, C Langford, C Lawrence, R Leander, K Lee, J-M Lee, NR Li, M Li, X Li, Y Liang, J Liju, S Lim, W-Y Lind, L Lindgren, CM Lindholm, E Liu, C-T Liu, JJ Lobbens, S Long, J Loos, RJF Lu, W Luan, J Lyssenko, V Ma, RCW Maeda, S Maegi, R Mannisto, S Matthews, DR Meigs, JB Melander, O Metspalu, A Meyer, J Mirza, G Mihailov, E Moebus, S Mohan, V Mohlke, KL Morris, AD Muehleisen, TW Mueller-Nurasyid, M Musk, B Nakamura, J Nakashima, E Navarro, P Peng-Keat, N Nica, AC Nilsson, PM Njolstad, I Noethen, MM Ohnaka, K Ong, TH Owen, KR Palmer, CNA Pankow, JS Park, KS Parkin, M Pechlivanis, S Pedersen, NL Peltonen, L Perry, JRB Peters, A Pinidiyapathirage, JM Platou, CGP Potter, S Price, JF Qi, L Radha, V Rallidis, L Rasheed, A Rathmann, W Rauramaa, R Raychaudhuri, S Rayner, NW Rees, SD Rehnberg, E Ripatti, S Robertson, N Roden, M Rossin, EJ Rudan, I Rybin, D Saaristo, TE Salomaa, V Saltevo, J Samuel, M Sanghera, DK Saramies, J Scott, J Scott, LJ Scott, RA Segre, AV Sehmi, J Sennblad, B Shah, N Shah, S Shera, AS Shu, XO Shuldiner, AR Sigurdsson, G Sijbrands, E Silveira, A Sim, X Sivapalaratnam, S Small, KS So, WY Stancakova, A Stefansson, K Steinbach, G Steinthorsdottir, V Stirrups, K Strawbridge, RJ Stringham, HM Sun, Q Suo, C Syvanen, A-C Takayanagi, R Takeuchi, F Tay, WT Teslovich, TM Thorand, B Thorleifsson, G Thorsteinsdottir, U Tikkanen, E Trakalo, J Tremoli, E Trip, MD Tsai, FJ Tuomi, T Tuomilehto, J Uitterlinden, AG Valladares-Salgado, A Vedantam, S Veglia, F Voight, BF Wang, C Wareham, NJ Wennauer, R Wickremasinghe, AR Wilsgaard, T Wilson, JF Wiltshire, S Winckler, W Wong, TY Wood, AR Wu, J-Y Wu, Y Yamamoto, K Yamauchi, T Yang, M Yengo, L Yokota, M Young, R Zabaneh, D Zhang, F Zhang, R Zheng, W Zimmet, PZ Altshuler, D Bowden, DW Cho, YS Cox, NJ Cruz, M Hanis, CL Kooner, J Lee, J-Y Seielstad, M Teo, YY Boehnke, M Parra, EJ Chambers, JC Tai, ES McCarthy, MI Morris, AP |
| Item Type: | Journal Article |
| Abstract: | To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. |
| Issue Date: | 1-Mar-2014 |
| Date of Acceptance: | 17-Jan-2014 |
| URI: | http://hdl.handle.net/10044/1/18309 |
| DOI: | 10.1038/ng.2897 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Research |
| Start Page: | 234 |
| End Page: | 244 |
| Journal / Book Title: | Nature Genetics |
| Volume: | 46 |
| Issue: | 3 |
| Copyright Statement: | © 2014 Nature America, Inc. All rights reserved. |
| Sponsor/Funder: | Medical Research Council (MRC) Medical Research Council (MRC) National Institute for Health Research |
| Funder's Grant Number: | G0801056 G1002084 NF-SI-0611-10136 |
| Keywords: | Science & Technology Life Sciences & Biomedicine Genetics & Heredity ASSOCIATION ANALYSES GLUCOSE-HOMEOSTASIS LOCI VARIANTS INDIVIDUALS CHROMATIN IDENTIFY Alleles Asian Continental Ancestry Group Case-Control Studies Diabetes Mellitus, Type 2 European Continental Ancestry Group Genetic Predisposition to Disease Genome-Wide Association Study Hispanic Americans Humans Polymorphism, Single Nucleotide Risk Factors DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium South Asian Type 2 Diabetes (SAT2D) Consortium Mexican American Type 2 Diabetes (MAT2D) Consortium Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium Humans Diabetes Mellitus, Type 2 Genetic Predisposition to Disease Risk Factors Case-Control Studies Polymorphism, Single Nucleotide Alleles Asian Continental Ancestry Group European Continental Ancestry Group Hispanic Americans Genome-Wide Association Study Science & Technology Life Sciences & Biomedicine Genetics & Heredity ASSOCIATION ANALYSES GLUCOSE-HOMEOSTASIS LOCI VARIANTS INDIVIDUALS CHROMATIN IDENTIFY 06 Biological Sciences 11 Medical and Health Sciences Developmental Biology |
| Publication Status: | Published |
| Online Publication Date: | 2014-02-09 |
| Appears in Collections: | Faculty of Medicine School of Public Health |