Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

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

Nat Genet 2014 Mar 9;46(3):234-44. Epub 2014 Feb 9.

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.

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http://dx.doi.org/10.1038/ng.2897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969612PMC
March 2014
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307 Citations
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