Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

Am J Hum Genet
Authors
Richa Saxena
Clara Elbers
Yiran Guo
Inga Peter
Tom Gaunt
Jessica Mega
Matthew Lanktree
Archana Tare
Berta Castillo
Yun Li
Toby Johnson
Marcel Bruinenberg
Diane Gilbert-Diamond
Ramakrishnan Rajagopalan
Benjamin Voight
Ashok Balasubramanyam
John Barnard
Florianne Bauer
Jens Baumert
Tushar Bhangale
Bernhard Böhm
Peter Braund
Paul Burton
Hareesh Chandrupatla
Robert Clarke
Rhonda Cooper-DeHoff
Errol Crook
George Davey-Smith
Ian Day
Anthonius de Boer
Mark de Groot
Fotios Drenos
Jane Ferguson
Caroline Fox
Clement Furlong
Quince Gibson
Christian Gieger
Lisa Gilhuijs-Pederson
Joseph Glessner
Anuj Goel
Yan Gong
Struan Grant
Diederick Grobbee
Claire Hastie
Steve Humphries
Cecilia Kim
Mika Kivimaki
Marcus Kleber
Christa Meisinger
Meena Kumari
Taimour Langaee
Debbie Lawlor
Mingyao Li
Maximilian Lobmeyer
Anke-Hilse van der Zee
Matthijs Meijs
Cliona Molony
David Morrow
Gurunathan Murugesan
Solomon Musani
Christopher Nelson
Stephen Newhouse
Jeffery O'Connell
Sandosh Padmanabhan
Jutta Palmen
Sanjey Patel
Carl Pepine
Mary Pettinger
Thomas Price
Suzanne Rafelt
Jane Ranchalis
Asif Rasheed
Elisabeth Rosenthal
Ingo Ruczinski
Sonia Shah
Haiqing Shen
Günther Silbernagel
Erin Smith
Annemieke Spijkerman
Alice Stanton
Michael Steffes
Barbara Thorand
Mieke Trip
Pim van der Harst
Daphne van der A
Erik van Iperen
Jessica van Setten
Jana van Vliet-Ostaptchouk
Niek Verweij
Bruce Wolffenbuttel
Taylor Young
M Hadi Zafarmand
Joseph Zmuda
Look AHEAD Research Group
DIAGRAM consortium
Michael Boehnke
David Altshuler
Mark McCarthy
W Kao
James Pankow
Thomas Cappola
Peter Sever
Neil Poulter
Mark Caulfield
Anna Dominiczak
Denis Shields
Deepak Bhatt
Deepak Bhatt
Li Zhang
Sean Curtis
John Danesh
Juan Casas
Yvonne van der Schouw
N Charlotte Onland-Moret
Pieter Doevendans
Gerald Dorn
Martin Farrall
Garret FitzGerald
Anders Hamsten
Robert Hegele
Aroon Hingorani
Marten Hofker
Gordon Huggins
Thomas Illig
Gail Jarvik
Julie Johnson
Olaf Klungel
William Knowler
Wolfgang Koenig
Winfried März
James Meigs
Olle Melander
Patricia Munroe
Braxton Mitchell
Susan Bielinski
Daniel Rader
Muredach Reilly
Stephen Rich
Jerome Rotter
Danish Saleheen
Nilesh Samani
Eric Schadt
Alan Shuldiner
Roy Silverstein
Kandice Kottke-Marchant
Philippa Talmud
Hugh Watkins
Folkert Asselbergs
Folkert Asselbergs
Paul de Bakker
Jeanne McCaffery
Cisca Wijmenga
Marc Sabatine
James Wilson
Alex Reiner
Donald Bowden
Hakon Hakonarson
David Siscovick
Brendan Keating
Keywords
Female
Humans
Male
Adult
Aged
Genetic Predisposition to Disease
Genotype
Middle Aged
Adolescent
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Young Adult
Case-Control Studies
Genetic Loci
Diabetes Mellitus, Type 2
Aged, 80 and over
Ethnic Groups
Follow-Up Studies
Abstract

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p

Year of Publication
2012
Journal
Am J Hum Genet
Volume
90
Issue
3
Pages
410-25
Date Published
2012 Mar 09
ISSN
1537-6605
URL
http://linkinghub.elsevier.com/retrieve/pii/S0002-9297(12)00031-6
DOI
10.1016/j.ajhg.2011.12.022
PubMed ID
22325160
PubMed Central ID
PMC3309185
Links
Grant list
G9521010 / Medical Research Council / United Kingdom
PG/09/022/26739 / British Heart Foundation / United Kingdom
RG/08/008/25291 / British Heart Foundation / United Kingdom
G0600705 / Medical Research Council / United Kingdom
G19/35 / Medical Research Council / United Kingdom
G0100222 / Medical Research Council / United Kingdom
U01 GM074492 / GM / NIGMS NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
G8802774 / Medical Research Council / United Kingdom
G0902037 / Medical Research Council / United Kingdom
UL1 TR000124 / TR / NCATS NIH HHS / United States
MC_U137686857 / Medical Research Council / United Kingdom
R01 HL074730 / HL / NHLBI NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
090532 / Wellcome Trust / United Kingdom
N01HC65226 / HL / NHLBI NIH HHS / United States
R01 HL088577 / HL / NHLBI NIH HHS / United States
R21 DK089378 / DK / NIDDK NIH HHS / United States
RG/08/014/24067 / British Heart Foundation / United Kingdom
P30 DK017047 / DK / NIDDK NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States
RG/07/008/23674 / British Heart Foundation / United Kingdom
RG/10/12/28456 / British Heart Foundation / United Kingdom

Recent Broad Publications