Journal
NATURE GENETICS
Volume 40, Issue 5, Pages 638-645Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.120
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Funding
- Medical Research Council [MC_U106179471, G0601261, G0600705] Funding Source: researchfish
- National Institute for Health Research [DHCS/07/07/008] Funding Source: researchfish
- National Institutes of Health Research (NIHR) [DHCS/07/07/008] Funding Source: National Institutes of Health Research (NIHR)
- MRC [G0601261, G0600705] Funding Source: UKRI
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Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). 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 similar to 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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