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

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 ana...

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Main Authors: Zeggini, E, Scott, L, Saxena, R, Voight, B, Marchini, J, Hu, T, de Bakker, P, Abecasis, G, Almgren, P, Andersen, G, Ardlie, K, Boström, K, Bergman, R, Bonnycastle, L, Borch-Johnsen, K, Burtt, N, Chen, H, Chines, P, Daly, M, Deodhar, P, Ding, C, Doney, A, Duren, W, Elliott, K, Erdos, MR
Format: Journal article
Language:English
Published: 2008
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author Zeggini, E
Scott, L
Saxena, R
Voight, B
Marchini, J
Hu, T
de Bakker, P
Abecasis, G
Almgren, P
Andersen, G
Ardlie, K
Boström, K
Bergman, R
Bonnycastle, L
Borch-Johnsen, K
Burtt, N
Chen, H
Chines, P
Daly, M
Deodhar, P
Ding, C
Doney, A
Duren, W
Elliott, K
Erdos, MR
author_facet Zeggini, E
Scott, L
Saxena, R
Voight, B
Marchini, J
Hu, T
de Bakker, P
Abecasis, G
Almgren, P
Andersen, G
Ardlie, K
Boström, K
Bergman, R
Bonnycastle, L
Borch-Johnsen, K
Burtt, N
Chen, H
Chines, P
Daly, M
Deodhar, P
Ding, C
Doney, A
Duren, W
Elliott, K
Erdos, MR
author_sort Zeggini, E
collection OXFORD
description 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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spelling oxford-uuid:85cb7672-4203-4a99-b3ba-55c4ab26e5932022-03-26T21:59:51ZMeta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:85cb7672-4203-4a99-b3ba-55c4ab26e593EnglishSymplectic Elements at Oxford2008Zeggini, EScott, LSaxena, RVoight, BMarchini, JHu, Tde Bakker, PAbecasis, GAlmgren, PAndersen, GArdlie, KBoström, KBergman, RBonnycastle, LBorch-Johnsen, KBurtt, NChen, HChines, PDaly, MDeodhar, PDing, CDoney, ADuren, WElliott, KErdos, MRGenome-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.
spellingShingle Zeggini, E
Scott, L
Saxena, R
Voight, B
Marchini, J
Hu, T
de Bakker, P
Abecasis, G
Almgren, P
Andersen, G
Ardlie, K
Boström, K
Bergman, R
Bonnycastle, L
Borch-Johnsen, K
Burtt, N
Chen, H
Chines, P
Daly, M
Deodhar, P
Ding, C
Doney, A
Duren, W
Elliott, K
Erdos, MR
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
title Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
title_full Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
title_fullStr Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
title_full_unstemmed Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
title_short Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
title_sort meta analysis of genome wide association data and large scale replication identifies additional susceptibility loci for type 2 diabetes
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