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Nature Genetics

Publication date: 2014-03-01
Volume: 46 Pages: 234 -
Publisher: Nature Research

Author:

Mahajan, Anubha
Go, Min Jin ; Zhang, Weihua ; Below, Jennifer E ; Gaulton, Kyle J ; Ferreira, Teresa ; Horikoshi, Momoko ; Johnson, Andrew D ; Ng, Maggie CY ; Prokopenko, Inga ; Saleheen, Danish ; Wang, Xu ; Zeggini, Eleftheria ; Abecasis, Goncalo R ; Adair, Linda S ; Almgren, Peter ; Atalay, Mustafa ; Aung, Tin ; Baldassarre, Damiano ; Balkau, Beverley ; Bao, Yuqian ; Barnett, Anthony H ; Barroso, Ines ; Basit, Abdul ; Been, Latonya F ; Beilby, John ; Bell, Graeme I ; Benediktsson, Rafn ; Bergman, Richard N ; Boehm, Bernhard O ; Boerwinkle, Eric ; Bonnycastle, Lori L ; Burtt, Noel ; Cai, Qiuyin ; Campbell, Harry ; Carey, Jason ; Cauchi, Stephane ; Caulfield, Mark ; Chan, Juliana CN ; Chang, Li-Ching ; Chang, Tien-Jyun ; Chang, Yi-Cheng ; Charpentier, Guillaume ; Chen, Chien-Hsiun ; Chen, Han ; Chen, Yuan-Tsong ; Chia, Kee-Seng ; Chidambaram, Manickam ; Chines, Peter S ; Cho, Nam H ; Cho, Young Min ; Chuang, Lee-Ming ; Collins, Francis S ; Cornelis, Marilyn C ; Couper, David J ; Crenshaw, Andrew T ; van Dam, Rob M ; Danesh, John ; Das, Debashish ; de Faire, Ulf ; Dedoussis, George ; Deloukas, Panos ; Dimas, Antigone S ; Dina, Christian ; Doney, Alex SF ; Donnelly, Peter J ; Dorkhan, Mozhgan ; van Duijn, Cornelia ; Dupuis, Josee ; Edkins, Sarah ; Elliott, Paul ; Emilsson, Valur ; Erbel, Raimund ; Eriksson, Johan G ; Escobedo, Jorge ; Esko, Tonu ; Eury, Elodie ; Florez, Jose C ; Fontanillas, Pierre ; Forouhi, Nita G ; Forsen, Tom ; Fox, Caroline ; Fraser, Ross M ; Frayling, Timothy M ; Froguel, Philippe ; Frossard, Philippe ; Gao, Yutang ; Gertow, Karl ; Gieger, Christian ; Gigante, Bruna ; Grallert, Harald ; Grant, George B ; Groop, Leif C ; Groves, Christopher J ; Grundberg, Elin ; Guiducci, Candace ; Hamsten, Anders ; Han, Bok-Ghee ; Hara, Kazuo ; Hassanali, Neelam ; Hattersley, Andrew T ; Hayward, Caroline ; Hedman, Asa K ; Herder, Christian ; Hofman, Albert ; Holmen, Oddgeir L ; Hovingh, Kees ; Hreidarsson, Astradur B ; Hu, Cheng ; Hu, Frank B ; Hui, Jennie ; Humphries, Steve E ; Hunt, Sarah E ; Hunter, David J ; Hveem, Kristian ; Hydrie, Zafar I ; Ikegami, Hiroshi ; Illig, Thomas ; Ingelsson, Erik ; Islam, Muhammed ; Isomaa, Bo ; Jackson, Anne U ; Jafar, Tazeen ; James, Alan ; Jia, Weiping ; Joeckel, Karl-Heinz ; Jonsson, Anna ; Jowett, Jeremy BM ; Kadowaki, Takashi ; Kang, Hyun Min ; Kanoni, Stavroula ; Kao, Wen Hong L ; Kathiresan, Sekar ; Kato, Norihiro ; Katulanda, Prasad ; Keinanen-Kiukaanniemi, Sirkka M ; Kelly, Ann M ; Khan, Hassan ; Khaw, Kay-Tee ; Khor, Chiea-Chuen ; Kim, Hyung-Lae ; Kim, Sangsoo ; Kim, Young Jin ; Kinnunen, Leena ; Klopp, Norman ; Kong, Augustine ; Korpi-Hyovalti, Eeva ; Kowlessur, Sudhir ; Kraft, Peter ; Kravic, Jasmina ; Kristensen, Malene M ; Krithika, S ; Kumar, Ashish ; Kumate, Jesus ; Kuusisto, Johanna ; Kwak, Soo Heon ; Laakso, Markku ; Lagou, Vasiliki ; Lakka, Timo A ; Langenberg, Claudia ; Langford, Cordelia ; Lawrence, Robert ; Leander, Karin ; Lee, Jen-Mai ; Lee, Nanette R ; Li, Man ; Li, Xinzhong ; Li, Yun ; Liang, Junbin ; Liju, Samuel ; Lim, Wei-Yen ; Lind, Lars ; Lindgren, Cecilia M ; Lindholm, Eero ; Liu, Ching-Ti ; Liu, Jian Jun ; Lobbens, Stephane ; Long, Jirong ; Loos, Ruth JF ; Lu, Wei ; Luan, Jian'an ; Lyssenko, Valeriya ; Ma, Ronald CW ; Maeda, Shiro ; Maegi, Reedik ; Mannisto, Satu ; Matthews, David R ; Meigs, James B ; Melander, Olle ; Metspalu, Andres ; Meyer, Julia ; Mirza, Ghazala ; Mihailov, Evelin ; Moebus, Susanne ; Mohan, Viswanathan ; Mohlke, Karen L ; Morris, Andrew D ; Muehleisen, Thomas W ; Mueller-Nurasyid, Martina ; Musk, Bill ; Nakamura, Jiro ; Nakashima, Eitaro ; Navarro, Pau ; Peng-Keat, Ng ; Nica, Alexandra C ; Nilsson, Peter M ; Njolstad, Inger ; Noethen, Markus M ; Ohnaka, Keizo ; Ong, Twee Hee ; Owen, Katharine R ; Palmer, Colin NA ; Pankow, James S ; Park, Kyong Soo ; Parkin, Melissa ; Pechlivanis, Sonali ; Pedersen, Nancy L ; Peltonen, Leena ; Perry, John RB ; Peters, Annette ; Pinidiyapathirage, Janani M ; Platou, Carl GP ; Potter, Simon ; Price, Jackie F ; Qi, Lu ; Radha, Venkatesan ; Rallidis, Loukianos ; Rasheed, Asif ; Rathmann, Wolfgang ; Rauramaa, Rainer ; Raychaudhuri, Soumya ; Rayner, N William ; Rees, Simon D ; Rehnberg, Emil ; Ripatti, Samuli ; Robertson, Neil ; Roden, Michael ; Rossin, Elizabeth J ; Rudan, Igor ; Rybin, Denis ; Saaristo, Timo E ; Salomaa, Veikko ; Saltevo, Juha ; Samuel, Maria ; Sanghera, Dharambir K ; Saramies, Jouko ; Scott, James ; Scott, Laura J ; Scott, Robert A ; Segre, Ayellet V ; Sehmi, Joban ; Sennblad, Bengt ; Shah, Nabi ; Shah, Sonia ; Shera, A Samad ; Shu, Xiao Ou ; Shuldiner, Alan R ; Sigurdsson, Gunnar ; Sijbrands, Eric ; Silveira, Angela ; Sim, Xueling ; Sivapalaratnam, Suthesh ; Small, Kerrin S ; So, Wing Yee ; Stancakova, Alena ; Stefansson, Kari ; Steinbach, Gerald ; Steinthorsdottir, Valgerdur ; Stirrups, Kathleen ; Strawbridge, Rona J ; Stringham, Heather M ; Sun, Qi ; Suo, Chen ; Syvanen, Ann-Christine ; Takayanagi, Ryoichi ; Takeuchi, Fumihiko ; Tay, Wan Ting ; Teslovich, Tanya M ; Thorand, Barbara ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Tikkanen, Emmi ; Trakalo, Joseph ; Tremoli, Elena ; Trip, Mieke D ; Tsai, Fuu Jen ; Tuomi, Tiinamaija ; Tuomilehto, Jaakko ; Uitterlinden, Andre G ; Valladares-Salgado, Adan ; Vedantam, Sailaja ; Veglia, Fabrizio ; Voight, Benjamin F ; Wang, Congrong ; Wareham, Nicholas J ; Wennauer, Roman ; Wickremasinghe, Ananda R ; Wilsgaard, Tom ; Wilson, James F ; Wiltshire, Steven ; Winckler, Wendy ; Wong, Tien Yin ; Wood, Andrew R ; Wu, Jer-Yuarn ; Wu, Ying ; Yamamoto, Ken ; Yamauchi, Toshimasa ; Yang, Mingyu ; Yengo, Loic ; Yokota, Mitsuhiro ; Young, Robin ; Zabaneh, Delilah ; Zhang, Fan ; Zhang, Rong ; Zheng, Wei ; Zimmet, Paul Z ; Altshuler, David ; Bowden, Donald W ; Cho, Yoon Shin ; Cox, Nancy J ; Cruz, Miguel ; Hanis, Craig L ; Kooner, Jaspal ; Lee, Jong-Young ; Seielstad, Mark ; Teo, Yik Ying ; Boehnke, Michael ; Parra, Esteban J ; Chambers, John C ; Tai, E Shyong ; McCarthy, Mark I ; Morris, Andrew P

Keywords:

Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, ASSOCIATION ANALYSES, GLUCOSE-HOMEOSTASIS, LOCI, VARIANTS, INDIVIDUALS, CHROMATIN, IDENTIFY, Alleles, Asian People, Case-Control Studies, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Risk Factors, White People, 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, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 3001 Agricultural biotechnology, 3102 Bioinformatics and computational biology, 3105 Genetics

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.