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

Research output: Contribution to journalArticle

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.

Details

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
  • Noel 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
  • Marilyn 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. F. Doney
  • Peter J. Donnelly
  • Cornelia van Duijn
  • Josee 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
  • Christopher 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 Joeckel
  • Anna Jonsson
  • Jeremy B. M. Jowett
  • Takashi Kadowaki
  • Hyun Min Kang
  • Stavroula Kanoni
  • Wen Hong L. Kao
  • Sekar Kathiresan
  • Norihiro Kato
  • Prasad Katulanda
  • Sirkka 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-Hyovalti
  • Sudhir Kowlessur
  • Peter Kraft
  • 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
  • Ching-Ti Liu
  • Jian Jun Liu
  • Stephane Lobbens
  • Jirong Long
  • Ruth J. F. Loos
  • Wei Lu
  • Jian'an Luan
  • Ronald C. W. Ma
  • Shiro Maeda
  • Reedik Maegi
  • Satu Mannisto
  • David R. Matthews
  • James B. Meigs
  • Andres Metspalu
  • Julia Meyer
  • Ghazala Mirza
  • Evelin Mihailov
  • Susanne Moebus
  • Viswanathan Mohan
  • Karen L. Mohlke
  • Andrew D. Morris
  • Thomas W. Muehleisen
  • Martina Mueller-Nurasyid
  • Bill Musk
  • Jiro Nakamura
  • Eitaro Nakashima
  • Pau Navarro
  • Peng-Keat Ng
  • Alexandra C. Nica
  • Inger Njolstad
  • Markus M. Noethen
  • 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
  • Janani M. Pinidiyapathirage
  • Carl G. P. Platou
  • Simon Potter
  • Jackie F. Price
  • Lu Qi
  • Venkatesan Radha
  • Loukianos Rallidis
  • Asif Rasheed
  • Wolfgang Rathmann
  • 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. Segre
  • Joban Sehmi
  • Bengt Sennblad
  • Nabi Shah
  • Sonia Shah
  • A. Samad Shera
  • Xiao Ou Shu
  • Alan R. Shuldiner
  • Gunnar Sigurdsson
  • Eric Sijbrands
  • Angela Silveira
  • Xueling Sim
  • Suthesh Sivapalaratnam
  • Kerrin S. Small
  • Wing Yee So
  • Alena Stancakova
  • Kari Stefansson
  • Gerald Steinbach
  • Valgerdur Steinthorsdottir
  • Kathleen Stirrups
  • Rona J. Strawbridge
  • Heather M. Stringham
  • Qi Sun
  • Chen Suo
  • Ann-Christine Syvanen
  • 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
  • John C. Chambers
  • E. Shyong Tai
  • Mark I. McCarthy
  • Andrew P. Morris
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)234
JournalNature Genetics
Volume46
Issue number3
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Diabetes and Endocrinology (013241530), Pediatrics/Urology/Gynecology/Endocrinology (013240400), Hypertension and Cardiovascular Disease (013242540), Internal Medicine Research Unit (013242520)