A genome-wide association study of type-2 diabetes in Iranians: the results of Bushehr Elderly Health (BEH) program

Type 2 diabetes mellitus (T2DM) is a growing global health concern, with limited genetic studies in the Iranian population. This study aimed to identify genetic variants associated with T2DM in elderly Iranians through a genome-wide association study (GWAS) in Bushehr. This GWAS was nested within the Bushehr Elderly Health Cohort Study, involving 2659 participants in Stage 1 and 2192 in Stage 2, all aged ≥ 60 years. T2DM was defined using fasting blood glucose, or hemoglobin A1c (HbA1c), or prior diagnosis with antidiabetic medication. Genotyping was performed using Infinium Global Screening Array (GSA) BeadChip (Illumina), with 9,186,584 SNPs retained after quality control. Associations were analyzed using a generalized linear mixed model, adjusted for age, sex, and principal components, with a significance threshold of p < 5 × 10⁻⁸. In Stage 1, SNP rs7903146-T in the TCF7L2 gene on chromosome 10q25.2 was significantly associated with T2DM ( β = 0.34, p = 2.3 × 10⁻⁸). In Stage 2, SNP rs7911322 in the ARHGAP19-SLIT1 gene on chromosome 10 showed a statistically significant association with T2DM ( β = 0.41, p = 4.6 × 10⁻⁸). A near-significant association was observed for rs6996001 in the ASAP1 gene ( p = 3.9 × 10⁻⁷) in Stage 1. This study confirms the role of TCF7L2 in T2DM and identifies potentially relevant loci within ARHGAP19-SLIT1 and ASAP1 in elderly Iranians. These findings highlight the importance of population-specific GWAS and warrant further replication and functional validation in larger independent cohorts.