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...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
2008
|
_version_ | 1797079681712783360 |
---|---|
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. |
first_indexed | 2024-03-07T00:49:14Z |
format | Journal article |
id | oxford-uuid:85cb7672-4203-4a99-b3ba-55c4ab26e593 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T00:49:14Z |
publishDate | 2008 |
record_format | dspace |
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 |
work_keys_str_mv | AT zegginie metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT scottl metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT saxenar metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT voightb metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT marchinij metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT hut metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT debakkerp metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT abecasisg metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT almgrenp metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT anderseng metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT ardliek metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT bostromk metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT bergmanr metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT bonnycastlel metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT borchjohnsenk metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT burttn metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT chenh metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT chinesp metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT dalym metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT deodharp metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT dingc metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT doneya metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT durenw metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT elliottk metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes AT erdosmr metaanalysisofgenomewideassociationdataandlargescalereplicationidentifiesadditionalsusceptibilitylocifortype2diabetes |