Open AccessGenome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
Author(s) -
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,
Gonçalo R. Abecasis,
Linda S. Adair,
Peter Almgren,
Mustafa Atalay,
Tin Aung,
Damiano Baldassarre,
Beverley Balkau,
Yuqian Bao,
Anthony Barnett,
Inês Barroso,
Abdul Basit,
Latonya Been,
John Beilby,
Graeme I. Bell,
Rafn Benediktsson,
Richard N. Bergman,
Bernhard O. Boehm,
Eric Boerwinkle,
Lori L. Bonnycastle,
Noël P. Burtt,
Qiuyin Cai,
Harry Campbell,
Jason Carey,
Stéphane Cauchi,
Mark J. Caulfield,
Juliana C.N. Chan,
Li-Ching Chang,
TienJyun Chang,
YiCheng Chang,
G. Charpentier,
Chien-Hsiun Chen,
Han Chen,
Yuan-Tsong Chen,
KeeSeng Chia,
Manickam Chidambaram,
Peter S. Chines,
Nam H. Cho,
Young Min Cho,
LeeMing Chuang,
Francis S. Collins,
Marilyn C. Cornelis,
David Couper,
Andrew Crenshaw,
Rob M. van Dam,
John Danesh,
Debashish Das,
Ulf dé Fairé,
George Dedoussis,
Panos Deloukas,
Antigone S. Dimas,
Christian Dina,
Alex S. F. Doney,
Peter Donnelly,
Mozhgan Dorkhan,
Cornelia M. van Duijn,
Josée Dupuis,
Sarah Edkins,
Paul Elliott,
Valur Emilsson,
Raimund Erbel,
Johan G. Eriksson,
Jorge Escobedo,
Tõnu Esko,
Elodie Eury,
José C. Florez,
Pierre Fontanillas,
Nita G. Forouhi,
Tom Forsén,
Caroline S. Fox,
Ross M. Fraser,
Timothy M. Frayling,
Philippe Froguel,
Philippe Frossard,
YuTang Gao,
Karl Gertow,
Christian Gieger,
Bruna Gigante,
Harald Grallert,
George Grant,
Leif Groop,
Christopher J. Groves,
Elin Grundberg,
Candace Guiducci,
Anders Hamsten,
BokGhee Han,
Kazuo Hara,
Neelam Hassanali,
Andrew T. Hattersley,
Caroline Hayward,
Åsa K. Hedman,
Christian Herder,
Albert Hofman,
Oddgeir L. Holmen,
Kees Hovingh,
Ástráður B. Hreiðarsson,
Cheng Hu,
Frank B. Hu,
Jennie Hui,
Steve E. Humphries,
Sarah Hunt,
David J. Hunter,
Kristian Hveem,
Muhammad Zafar Iqbal Hydrie,
Hiroshi Ikegami,
Thomas Illig,
Erik Ingelsson,
Muhammed Islam,
Bo Isomaa,
Anne Jackson,
Tazeen Jafar,
Anthony James,
Weiping Jia,
KarlHeinz Jöckel,
Anna Jonsson,
Jeremy B. M. Jowett,
Takashi Kadowaki,
Hyun Min Kang,
Stavroula Kai,
Wen Hong Linda Kao,
Sekar Kathiresan,
Norihiro Kato,
Prasad Katulanda,
Sirkka KeinänenKiukaanniemi,
Ann M Kelly,
Hassan Khan,
KayTee Khaw,
Chiea Chuen Khor,
Hyung-Lae Kim,
Sang Soo Kim,
Young Jin Kim,
Leena Kinnunen,
Norman Klopp,
Augustine Kong,
Eeva Korpi-Hyövälti,
Sudhir Kowlessur,
Peter Kraft,
Jasmina Kravić,
Malene M. Kristensen,
S. Krithika,
Ashish Kumar,
J Kumate,
Johanna Kuusisto,
Soo Heon Kwak,
Markku Laakso,
Vasiliki Lagou,
Timo A. Lakka,
Claudia Langenberg,
Cordelia Langford,
Robert Lawrence,
Karin Leander,
Jen-Mai Lee,
Sang Lee,
Man Li,
Yun Li,
Junbin Liang,
Samuel Liju,
WeiYen Lim,
Lars Lind,
Cecilia M. Lindgren,
Eero Lindholm,
Yongmei Liu,
Jianjun Liu,
Stéphane Lobbens,
Jirong Long,
Ruth J. F. Loos,
Wei Lu,
Jian’an Luan,
Valeriya Lyssenko,
Ronald C.W.,
Shiro Maeda,
Reedik Mägi,
Satu Männistö,
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,
HaeWon Uh,
Martina MüllerNurasyid,
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,
Nicholette D. Palmer,
James S. Pankow,
Kyong Soo Park,
Melissa Parkin,
Sonali Pechlivanis,
Nancy L. Pedersen,
Leena Peltonen,
John R. B. Perry,
Annette Peters,
Janani Pinidiyapathirage,
Carl Platou,
Simon Potter,
Jackie F. Price,
Lu Qi,
Venkatesan Radha,
Lοukianos S. Rallidis,
Asif Rasheed,
Wolfgang Rathmann,
Rainer Rauramaa,
Soumya Raychaudhuri,
Nigel W. Rayner,
Simon D. Rees,
Emil Rehnberg,
Samuli Ripatti,
Neil Robertson,
Michael Roden,
Elizabeth J. Rossin,
Igor Rudan,
Denis Rybin,
Timo 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 Sigurðsson,
Eric J.G. Sijbrands,
Angela Silveira,
Xueling Sim,
Suthesh Sivapalaratnam,
Kerrin S. Small,
Wing Yee So,
Alena Stančáková,
Kári Stéfansson,
Gerald Steinbach,
Valgerður Steinthórsdóttir,
Kathleen Stirrups,
Rona J. Strawbridge,
Heather M. Stringham,
Qi Sun,
Chen Suo,
AnnChristine Syvänen,
Ryoichi Takayanagi,
Fumihiko Takeuchi,
Wan Ting Tay,
Tanya M. Teslovich,
Barbara Thorand,
Guðmar Þorleifsson,
Unnur Þorsteinsdóttir,
Emmi Tikkanen,
Joseph Trakalo,
Elena Tremoli,
Mieke D. Trip,
Fuu Jen Tsai,
Jaakko Tuomilehto,
André G. Uitterlinden,
Adán ValladaresSalgado,
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,
JerYuarn Wu,
Ying Wu,
Ken Yamamoto,
Toshimasa Yamauchi,
MingYu Yang,
Loïc Yengo,
Mitsuhiro Yokota,
Robin Young,
Delilah Zabaneh,
Fan Zhang,
Rong Zhang,
Wei Zheng,
Paul Zimmet,
David Altshuler,
Donald W. Bowden,
Yoon Shin Cho,
Nancy J. Cox,
Miguel Cruz,
Craig L. Hanis,
Jaspal S. Kooner,
JongYoung Lee,
Mark Seielstad,
Yik Ying Teo,
Michael Boehnke,
Esteban J. Parra,
John C. Chambers,
E Shyong Tai,
Mark I. McCarthy,
Andrew P. Morris
Publication year - 2014
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/ng.2897
Subject(s) - genome wide association study , biology , genetic architecture , genetic association , genetics , single nucleotide polymorphism , genetic genealogy , allele , 1000 genomes project , meta analysis , trait , evolutionary biology , quantitative trait locus , gene , genotype , population , medicine , environmental health , computer science , programming language
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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