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June 25, 2026European journal of medical research0 citationsOpen Access

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

MBMohammad BidkhoriAAAlireza AzarbooSJSayeh Jalali

Key Result

The SNP rs7903146-T in the TCF7L2 gene was significantly associated with type 2 diabetes in elderly Iranians (β=0.34, p=2.3×10⁻⁸).

Key Points

  • This research aims to identify genetic variants associated with type 2 diabetes mellitus in elderly Iranians.
  • Conducted a genome-wide association study with two stages involving 2659 participants in Stage 1 and 2192 in Stage 2, all aged ≥ 60 years.
  • Genotyping performed using Infinium Global Screening Array BeadChip, retaining 9,186,584 SNPs after quality control.
  • Associations analyzed using a generalized linear mixed model, adjusted for age, sex, and principal components.
  • SNP rs7903146-T in the TCF7L2 gene associated with T2DM in Stage 1 (β = 0.34, p = 2.3 × 10⁻⁸).
  • SNP rs7911322 in the ARHGAP19-SLIT1 gene showed association with T2DM in Stage 2 (β = 0.41, p = 4.6 × 10⁻⁸).
  • Near-significant association for rs6996001 in the ASAP1 gene in Stage 1 (p = 3.9 × 10⁻⁷).

Study Design

Type

Cohort (n=2,659)

Multicenter

No

Structured PICO

P
Population
2,659 elderly Iranian adults aged 60 years and older from the Bushehr Elderly Health Cohort Study evaluated for genetic variants associated with type 2 diabetes.
O
Outcome
Type 2 Diabetes Mellitus (T2DM) defined by fasting blood glucose ≥126 mg/dL, prior diagnosis with antidiabetic medication, or (in Stage 2) hemoglobin A1c (HbA1c) ≥6.5%

This genome-wide association study in elderly Iranians confirms the established role of the TCF7L2 gene in Type 2 Diabetes and identifies novel potential susceptibility loci in ARHGAP19-SLIT1 and ASAP1.

Main Result

Effect estimate: β=0.34

p-value: p=2.3×10⁻⁸

Limitations

  • Requires further replication and functional validation in larger independent cohorts
  • Attenuated significance in the fully adjusted model for ARHGAP19-SLIT1 suggests possible population-specific effects or confounding
  • Requires replication and functional validation in larger independent cohorts

Abstract

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.

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Cite This Study

Bidkhori et al. (2026) conducted a cohort in Type 2 Diabetes Mellitus (n=2,659). Genetic variants (SNPs) vs. Non-carriers / Reference alleles was evaluated on Association of SNPs with Type 2 Diabetes Mellitus (β=0.34, p=2.3×10⁻⁸). The SNP rs7903146-T in the TCF7L2 gene was significantly associated with type 2 diabetes in elderly Iranians (β=0.34, p=2.3×10⁻⁸).

synapsesocial.com/papers/6a3d91e2408ebb922448b1e4https://doi.org/10.1186/s40001-026-04740-y
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