Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Eleftheria Zeggini; Laura J Scott; Richa Saxena; Benjamin F Voight; Jonathan L Marchini; Tianle Hu; Paul I W de Bakker; Gonçalo R Abecasis; Peter Almgren; Gitte Andersen; Kristin Ardlie; Kristina Bengtsson Boström; Richard N Bergman; Lori L Bonnycastle; Knut Borch-Johnsen; Noël P Burtt; Hong Chen; Peter S Chines; Mark J Daly; Parimal Deodhar; Chia-Jen Ding; Alex S F Doney; William L Duren; Katherine S Elliott; Michael R Erdos; Timothy M Frayling; Rachel M Freathy; Lauren Gianniny; Harald Grallert; Niels Grarup; Christopher J Groves; Candace Guiducci; Torben Hansen; Christian Herder; Graham A Hitman; Thomas E Hughes; Bo Isomaa; Anne U Jackson; Torben Jørgensen; Augustine Kong; Kari Kubalanza; Finny G Kuruvilla; Johanna Kuusisto; Claudia Langenberg; Hana Lango; Torsten Lauritzen; Yun Li; Cecilia M Lindgren; Valeriya Lyssenko; Amanda F Marvelle; Christa Meisinger; Kristian Midthjell; Karen L Mohlke; Mario A Morken; Andrew D Morris; Narisu Narisu; Peter Nilsson; Katharine R Owen; Colin N A Palmer; Felicity Payne; John R B Perry; Elin Pettersen; Carl Platou; Inga Prokopenko; Lu Qi; Li Qin; Nigel W Rayner; Matthew Rees; Jeffrey J Roix; Anelli Sandbaek; Beverley Shields; Marketa Sjögren; Valgerdur Steinthorsdottir; Heather M Stringham; Amy J Swift; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Nicholas J Timpson; Tiinamaija Tuomi; Jaakko Tuomilehto; Mark Walker; Richard M Watanabe; Michael N Weedon; Cristen J Willer; Thomas Illig; Kristian Hveem; Frank B Hu; Markku Laakso; Kari Stefansson; Oluf Pedersen; Nicholas J Wareham; Inês Barroso; Andrew T Hattersley; Francis S Collins; Leif Groop; Mark I McCarthy; Michael Boehnke; David Altshuler; Wellcome Trust Case Control Consortium

doi:10.1038/ng.120

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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Journal article

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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Eleftheria Zeggini, Laura J Scott, Richa Saxena, Benjamin F Voight, Jonathan L Marchini, Tianle Hu, Paul I W de Bakker, Gonçalo R Abecasis, Peter Almgren, Gitte Andersen, …

Nature genetics, Vol.40(5), pp.638-645

01/05/2008

DOI: https://doi.org/10.1038/ng.120

PMID: 18372903

Abstract

Diabetes Mellitus, Type 2 - genetics

Genetic Predisposition to Disease

Genome, Human

Humans

Polymorphism, Single Nucleotide

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

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Title: Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
Creators: Eleftheria Zeggini - University of Oxford
Laura J Scott - University of Michigan–Ann Arbor
Richa Saxena - Broad Institute
Benjamin F Voight - Massachusetts Institute of Technology
Jonathan L Marchini - University of Oxford
Tianle Hu - University of Michigan–Ann Arbor
Paul I W de Bakker - Broad Institute
Gonçalo R Abecasis - University of Michigan–Ann Arbor
Peter Almgren - Malmö University
Gitte Andersen
Kristin Ardlie - Broad Institute
Kristina Bengtsson Boström - Skaraborg Hospital
Richard N Bergman - University of Southern California
Lori L Bonnycastle - National Human Genome Research Institute
Knut Borch-Johnsen
Noël P Burtt - Broad Institute
Hong Chen - Boston Biomedical Research Institute
Peter S Chines - National Human Genome Research Institute
Mark J Daly - Broad Institute
Parimal Deodhar - National Human Genome Research Institute
Chia-Jen Ding - University of Michigan–Ann Arbor
Alex S F Doney - Ninewells Hospital
William L Duren - University of Michigan–Ann Arbor
Katherine S Elliott - University of Oxford
Michael R Erdos - National Human Genome Research Institute
Timothy M Frayling - Peninsula College of Medicine and Dentistry
Rachel M Freathy - Peninsula College of Medicine and Dentistry
Lauren Gianniny - Massachusetts Institute of Technology
Harald Grallert - Institute of Groundwater Ecology
Niels Grarup - Steno Diabetes Center
Christopher J Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Candace Guiducci - Massachusetts Institute of Technology
Torben Hansen - Steno Diabetes Center
Christian Herder - Deutsches Diabetes-Zentrum e.V.
Graham A Hitman - Royal London Hospital
Thomas E Hughes - Boston Biomedical Research Institute
Bo Isomaa
Anne U Jackson - University of Michigan–Ann Arbor
Torben Jørgensen - Glostrup Hospital
Augustine Kong - deCODE Genetics
Kari Kubalanza - National Human Genome Research Institute
Finny G Kuruvilla - Massachusetts General Hospital
Johanna Kuusisto - Kuopio University Hospital
Claudia Langenberg - MRC Epidemiology Unit
Hana Lango
Torsten Lauritzen - Aarhus University
Yun Li - University of Michigan–Ann Arbor
Cecilia M Lindgren - University of Oxford
Valeriya Lyssenko - Lund University
Amanda F Marvelle - University of North Carolina at Chapel Hill
Christa Meisinger - Institute of Groundwater Ecology
Kristian Midthjell - Norwegian University of Science and Technology
Karen L Mohlke - University of North Carolina at Chapel Hill
Mario A Morken - National Human Genome Research Institute
Andrew D Morris - Ninewells Hospital
Narisu Narisu - National Human Genome Research Institute
Peter Nilsson - Lund University
Katharine R Owen - University of Oxford
Colin N A Palmer
Felicity Payne - Wellcome Sanger Institute
John R B Perry - Peninsula College of Medicine and Dentistry
Elin Pettersen - Norwegian University of Science and Technology
Carl Platou
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Lu Qi - Harvard University
Li Qin
Nigel W Rayner - Oxford Centre for Diabetes, Endocrinology and Metabolism
Matthew Rees - National Human Genome Research Institute
Jeffrey J Roix - Boston Biomedical Research Institute
Anelli Sandbaek
Beverley Shields - Peninsula College of Medicine and Dentistry
Marketa Sjögren - Lund University
Valgerdur Steinthorsdottir
Heather M Stringham - University of Michigan–Ann Arbor
Amy J Swift - National Human Genome Research Institute
Gudmar Thorleifsson - deCODE Genetics
Unnur Thorsteinsdottir
Nicholas J Timpson - University of Bristol
Tiinamaija Tuomi
Jaakko Tuomilehto - Folkhälsans Forskningscentrum
Mark Walker - Newcastle University
Richard M Watanabe - University of Southern California
Michael N Weedon - Peninsula College of Medicine and Dentistry
Cristen J Willer - University of Michigan–Ann Arbor
Thomas Illig - Institute of Groundwater Ecology
Kristian Hveem - Norwegian University of Science and Technology
Frank B Hu - Harvard University
Markku Laakso - Kuopio University Hospital
Kari Stefansson - deCODE Genetics
Oluf Pedersen - Aarhus University
Nicholas J Wareham - Addenbrooke's Hospital
Inês Barroso - Wellcome Sanger Institute
Andrew T Hattersley - Peninsula College of Medicine and Dentistry
Francis S Collins - National Human Genome Research Institute
Leif Groop - University of Helsinki
Mark I McCarthy - Oxford Centre for Diabetes, Endocrinology and Metabolism
Michael Boehnke - University of Michigan–Ann Arbor
David Altshuler - Massachusetts General Hospital
Wellcome Trust Case Control Consortium
Publication Details: Nature genetics, Vol.40(5), pp.638-645
Date published: 01/05/2008
Grant note: DK072193 / NIDDK NIH HHS HL084729 / NHLBI NIH HHS R01 DK062370 / NIDDK NIH HHS DHCS/07/07/008 / Department of Health CA87969 / NCI NIH HHS R01 DK072193 / NIDDK NIH HHS R01 HG002651 / NHGRI NIH HHS HG002651 / NHGRI NIH HHS 072960 / Wellcome Trust 090532 / Wellcome Trust
Identifiers: 99928607002346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

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