Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.

Nat Genet
Authors
Benjamin Voight
Laura Scott
Valgerdur Steinthorsdottir
Andrew Morris
Christian Dina
Ryan Welch
Eleftheria Zeggini
Cornelia Huth
Yurii Aulchenko
Gudmar Thorleifsson
Laura McCulloch
Teresa Ferreira
Harald Grallert
Najaf Amin
Guanming Wu
Cristen Willer
Soumya Raychaudhuri
Steve McCarroll
Claudia Langenberg
Oliver Hofmann
Josée Dupuis
Lu Qi
Ayellet Segrè
Mandy van Hoek
Pau Navarro
Kristin Ardlie
Beverley Balkau
Rafn Benediktsson
Amanda Bennett
Roza Blagieva
Eric Boerwinkle
Lori Bonnycastle
Kristina Boström
Bert Bravenboer
Suzannah Bumpstead
Noisël Burtt
Guillaume Charpentier
Peter Chines
Marilyn Cornelis
David Couper
Gabe Crawford
Alex Doney
Katherine Elliott
Amanda Elliott
Michael Erdos
Caroline Fox
Christopher Franklin
Martha Ganser
Christian Gieger
Niels Grarup
Todd Green
Simon Griffin
Christopher Groves
Candace Guiducci
Samy Hadjadj
Neelam Hassanali
Christian Herder
Bo Isomaa
Anne Jackson
Paul Johnson
Torben Jørgensen
Wen Kao
Norman Klopp
Augustine Kong
Peter Kraft
Johanna Kuusisto
Torsten Lauritzen
Man Li
Aloysius Lieverse
Cecilia Lindgren
Valeriya Lyssenko
Michel Marre
Thomas Meitinger
Kristian Midthjell
Mario Morken
Narisu Narisu
Peter Nilsson
Katharine Owen
Felicity Payne
John Perry
Ann-Kristin Petersen
Carl Platou
Christine Proença
Inga Prokopenko
Wolfgang Rathmann
N William Rayner
Neil Robertson
Ghislain Rocheleau
Michael Roden
Michael Sampson
Richa Saxena
Beverley Shields
Peter Shrader
Gunnar Sigurdsson
Thomas Sparsø
Klaus Strassburger
Heather Stringham
Qi Sun
Amy Swift
Barbara Thorand
Jean Tichet
Tiinamaija Tuomi
Rob van Dam
Timon van Haeften
Thijs van Herpt
Jana van Vliet-Ostaptchouk
G Bragi Walters
Michael Weedon
Cisca Wijmenga
Jacqueline Witteman
Richard Bergman
Stephane Cauchi
Francis Collins
Anna Gloyn
Ulf Gyllensten
Torben Hansen
Winston Hide
Graham Hitman
Albert Hofman
David Hunter
Kristian Hveem
Markku Laakso
Karen Mohlke
Andrew Morris
Colin Palmer
Peter Pramstaller
Igor Rudan
Eric Sijbrands
Lincoln Stein
Jaakko Tuomilehto
Andre Uitterlinden
Mark Walker
Nicholas Wareham
Richard Watanabe
Gonçalo Abecasis
Bernhard Boehm
Harry Campbell
Mark Daly
Andrew Hattersley
Frank Hu
James Meigs
James Pankow
Oluf Pedersen
H-Erich Wichmann
Inês Barroso
Jose Florez
Timothy Frayling
Leif Groop
Rob Sladek
Unnur Thorsteinsdottir
James Wilson
Thomas Illig
Philippe Froguel
Cornelia van Duijn
Kari Stefansson
David Altshuler
Michael Boehnke
Mark McCarthy
MAGIC Investigators
GIANT Consortium
Keywords
Humans
Gene Expression Profiling
Genetic Predisposition to Disease
Gene Dosage
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Genome, Human
Blood Glucose
Diabetes Mellitus, Type 2
Genetic Heterogeneity
Fasting
Hepatocyte Nuclear Factor 1-alpha
Dual-Specificity Phosphatases
KCNQ1 Potassium Channel
Meta-Analysis as Topic
Mitogen-Activated Protein Kinase Phosphatases
Abstract

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
Year of Publication
2010
Journal
Nat Genet
Volume
42
Issue
7
Pages
579-89
Date Published
2010 Jul
ISSN
1546-1718
URL
DOI
10.1038/ng.609
PubMed ID
20581827
PubMed Central ID
PMC3080658
Links
Grant list
N01HC55020 / HL / NHLBI NIH HHS / United States
R01 DK078616 / DK / NIDDK NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
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N01-HC-25195 / HC / NHLBI NIH HHS / United States
CZB/4/710 / Chief Scientist Office / United Kingdom
R01 DK073490 / DK / NIDDK NIH HHS / United States
K08 AR055688-03 / AR / NIAMS NIH HHS / United States
R01 DK058845 / DK / NIDDK NIH HHS / United States
R56 DK062370 / DK / NIDDK NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
G0600331 / Medical Research Council / United Kingdom
079557 / Wellcome Trust / United Kingdom
R01HL59367 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
086596 / Wellcome Trust / United Kingdom
N01-HC-55022 / HC / NHLBI NIH HHS / United States
088885 / Wellcome Trust / United Kingdom
R01 HL059367 / HL / NHLBI NIH HHS / United States
K23-DK65978 / DK / NIDDK NIH HHS / United States
G0700222(81696) / Medical Research Council / United Kingdom
N01-HC-55016 / HC / NHLBI NIH HHS / United States
U01 HG004171 / HG / NHGRI NIH HHS / United States
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DK58845 / DK / NIDDK NIH HHS / United States
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N01HC55022 / HL / NHLBI NIH HHS / United States
DK069922 / DK / NIDDK NIH HHS / United States
U01HG004399 / HG / NHGRI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
075491 / Wellcome Trust / United Kingdom
DHCS/07/07/008 / Department of Health / United Kingdom
N01HC55015 / HL / NHLBI NIH HHS / United States
077016 / Wellcome Trust / United Kingdom
1K08AR055688 / AR / NIAMS NIH HHS / United States
083270 / Wellcome Trust / United Kingdom
R01 DK062370 / DK / NIDDK NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
072960 / Wellcome Trust / United Kingdom
K99 HL094535 / HL / NHLBI NIH HHS / United States
DK072193 / DK / NIDDK NIH HHS / United States
MC_U106179471 / Medical Research Council / United Kingdom
076113 / Wellcome Trust / United Kingdom
K24-DK080140 / DK / NIDDK NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01 DK029867 / DK / NIDDK NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
G0701863 / Medical Research Council / United Kingdom
K24 DK080140 / DK / NIDDK NIH HHS / United States
090532 / Wellcome Trust / United Kingdom
N01-HC-55020 / HC / NHLBI NIH HHS / United States
U01HG004171 / HG / NHGRI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
MC_U106179474 / Medical Research Council / United Kingdom
U01 DK078616 / DK / NIDDK NIH HHS / United States
1K99HL094535-01A1 / HL / NHLBI NIH HHS / United States
DK078616 / DK / NIDDK NIH HHS / United States
G0700222 / Medical Research Council / United Kingdom
064890 / Wellcome Trust / United Kingdom
U01 DK062370 / DK / NIDDK NIH HHS / United States
DK062370 / DK / NIDDK NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
Z01 HG000024 / HG / NHGRI NIH HHS / United States
MC_U127592696 / Medical Research Council / United Kingdom
K08 AR055688 / AR / NIAMS NIH HHS / United States
U54 DA021519 / DA / NIDA NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
DK073490 / DK / NIDDK NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
G0601261 / Medical Research Council / United Kingdom
U01 HG004399 / HG / NHGRI NIH HHS / United States
K23 DK065978 / DK / NIDDK NIH HHS / United States
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081682 / Wellcome Trust / United Kingdom
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