Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes

Abstract

Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 × 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.

Figure 1

Genome-wide plots of -log₁₀ P-values from stratified 1 df tests combining results from all three studies. Values of -log₁₀ P greater than 10 are plotted at 10. SNPs only present on the Illumina chip are shown in blue, those only present on the Affymetrix chip in red, and those present on both chips are shown in black. Points are plotted in the order red, blue, black. Previously known disease susceptibility loci are marked by vertical black lines, while new findings from the current analysis are marked by vertical grey lines (solid lines for convincingly replicated loci and dashed lines for nominally replicated results).