The type 2 diabetes risk rs11708067</span>-A allele showed fewer H3K27ac ChIP-seq reads in human islets, lower transcriptional activity in reporter assays in rodent β-cells (rat 832/13 and mouse MIN6), and increased nuclear protein binding compared with the rs11708067-G allele.
In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p = 9.1×10(-4)) and 1.16 (95% CI: 1.05, 1.29; p = 3.49×10(-3)) respectively.
Birthweight was inversely associated with the type 2 diabetes risk alleles of ADCY5 rs11708067 (beta = -33 g [95% CI -55, -10], p = 0.004) and CDKAL1 rs7756992 (beta = -22 g [95% CI -43, -1], p = 0.04).