Analysis of candidate genes on chromosome 20q12-13.1 reveals evidence for BMI mediated association of PREX1 with type 2 diabetes in European Americans

Chromosome 20q12-q13.1 has been linked to type 2 diabetes (T2D) in multiple populations. We examined the influence of genes in this region on T2D and BMI in two European American case–control populations. SNPs were genotyped in 300 diabetic patients and 310 controls. A subset of 72 SNPs were further genotyped in 470 cases and 442 controls. All genes examined showed evidence of association with T2D in the initial sample (additive P-value [Pa] = 0.00090–0.045). SNPs near PREX1 were also associated in the second case–control population (Pa = 0.017–0.042). The combined analysis resulted in the same SNPs, among others, associated with T2D (Pa = 0.0013–0.041). Stratification analysis by T2D status showed that association with BMI was observed solely in cases (Pa = 0.0018–0.041). Mediation testing revealed that 30–40% of the effects of these SNPs on T2D were significantly mediated by BMI. SNPs near PREX1 may contribute to T2D susceptibility mediated through effects of adiposity in European Americans.