A replication study of 19 GWAS-validated type 2 diabetes at-risk variants in the Lebanese population

Abstract

Aim Recent genome-wide association scans (GWAS) and replication studies have expanded the list of validated type 2 diabetes (T2DM) susceptibility loci. We replicated T2DM association of 19 SNPs from 15 candidate loci in Lebanese Arabs.

Methods Case–control association study, comprising 995 T2DM patients and 1076 control participants. We genotyped by the allelic discrimination method 19 SNPs in/near ADAM30, NOTCH2, THADA, TMEFF2, COL8A1, ADAMTS9-AS2, WFS1, JAZF1, SLC30A8, KCNQ1, LOC387761, ALX4, TSPAN8, FTO, and HNF1.

Results Allele frequencies of the tested SNPs were comparable with those of Caucasians. COL8A1 rs792837 (P = 2.9 × 10−9), KCNQ1 rs2237892 (P = 1.8 × 10−18) and rs2237895 (P = 0.002), ALX4 rs729287 (Pc = 7.5 × 10−5), and HNF1 rs4430796 (P = 0.003) were significantly associated with T2DM, with similar effect sizes to those of Europeans. While FTO rs8050136 and rs17817449, ADAMTS9 rs4607103, and WFS1 rs10010131 were initially associated with T2DM, this was lost upon multiple testing correction. The remaining variants were not associated with T2DM, possibly resulting from insufficient power to detect smaller allele effects.

Conclusion In addition to previous findings on the association of IGF2BP2, CDKAL1, TCF7L2 variants with T2DM among Lebanese, here we extend these by validating the association of five additional loci with T2DM in Lebanese Arabs.