Expression quantitative trait analyses to identify causal genetic variants for type 2 diabetes susceptibility

Figure 3 Prioritizing type 2 diabetes-associated variants by expression quantitative trait loci analysis: An example. HSD17B12 is one of 172 genes differentially expressed in adipose tissue of insulin-resistant (IR, n = 31) vs insulin-sensitive (IS, n = 31) subjects in a genome-wide study (A) by Elbein et al[76]. Its expression in subcutaneous adipose of non-diabetic subjects (n = 141) also shows a significant correlation (B) with insulin sensitivity (SI). Strongest cis-eSNP for adipose tissue (C) expression of HSD17B12 (in adipose eQTL from the MuTHER project)[55] is also associated with T2D (D) in a large GWAS meta-analysis (in DIAGRAM.v3 data from 12171 T2D and 56862 controls)[13]. This locus also includes a 3’UTR SNP rs1061810 that shows association (E) with T2D and expression of HSD17B12 (in qRT-PCR analysis in adipose tissue from 141 non-diabetic subjects). eSNP: Expression regulatory SNP; eQTL: Expression quantitative trait loci; T2D: Type 2 diabetes.