Abstract
BACKGROUND: Type 1 diabetes (T1D) is a severe and prevalent metabolic disease. Due to its high heredity, an increasing number of genome-wide association studies have been performed, most of which were from hospital-based case-control studies with a relatively small sample size. The association of single nucleotide polymorphisms (SNPs) and T1D has been less studied and is less understood in natural cohorts. AIM: To investigate the significant variants of T1D, which could be potential biomarkers for T1D prediction or even therapy. METHODS: A genome-wide association study (GWAS) of adult T1D was performed in a nested case-control study (785 cases vs 804 controls) from a larger 5-year cohort study in Suzhou, China. Potential harmful or protective SNPs were evaluated for T1D. Subsequent expression and splicing quantitative trait loci (eQTL and sQTL) analyses were carried out to identify target genes modulated by these SNPs. RESULTS: A harmful SNP for T1D, rs3117017 [odds ratio (OR) = 3.202, 95% confidence interval (CI): 2.296-4.466, P = 9.33 × 10(-4)] and three protective SNPs rs55846421 (0.113, 0.081-0.156, 1.76 × 10(-9)), rs75836320 (0.283, 0.205-0.392, 1.07 × 10(-4)), rs362071 (0.568, 0.495-0.651, 1.66 × 10(-4)) were identified. Twenty-two genes were further identified as potential candidates for T1D onset. CONCLUSION: We identified a potential genetic basis of T1D, both protective and harmful, using a GWAS in a larger nested case-control study of a Chinese population.