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

Wellcome Trust Case Control Consortium, For the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Eleftheria Zeggini, Laura J. Scott, Gitte Andersen, Knut Borch-Johnsen, Amanda F. Marvelle

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    Abstrakt

    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 ∼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 × 10-14), CDC123-CAMK1D (P = 1.2 × 10-10), TSPAN8-LGR5 (P = 1.1 × 10-9), THADA (P = 1.1 × 10-9), ADAMTS9 (P = 1.2 × 10-8) and NOTCH2 (P = 4.1 × 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.

    OriginalsprogEngelsk
    Sider (fra-til)638-645
    Antal sider8
    TidsskriftNature Genetics
    Vol/bind40
    Udgave nummer5
    DOI
    StatusUdgivet - 1 maj 2008

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