Aims: Recent meta-genome-wide association studies identified several genetic variants associated with beta-cell function in type 1 diabetes (T1D). The aim of this study was to investigate the associations between these variants and T1D risk, C-peptide levels, islet-specific autoantibodies, and lipid levels in Chinese Han population.
Methods: A total of 1005 unrelated autoantibody-positive T1D cases and 1417 healthy controls were included, which were genotyped for rs559047, rs9260151, and rs3135002. T1D individuals were measured for both C-peptide and lipid levels. Logistic regression models were used to examine these associations.
Results: We found that rs3135002 A allele showed a genome-wide significant association with T1D risk (OR = 0.22, 95% CI = 0.17-0.30; P = 7.49 × 10-27), and significant heterogeneity of effect size was observed between early-onset and later-onset T1D subgroups (I2 = 80% and P = 0.026). Rs559047 had a nominal association with fasting C-peptide levels in newly diagnosed T1D individuals (P = 0.036). Moreover, rs3135002 A allele was significantly associated with GADA positivity (OR = 0.52, 95% CI = 0.30-0.91, P = 0.02). In addition, nominal correlations were observed with HDL levels for rs559047 (P = 0.042), while LDL levels for rs9260151 (P = 0.032) in T1D individuals.
Conclusions: Our results indicate that there are both similarities and differences for the associations of genetic variants among T1D development, progression, and related autoimmunity, metabolic traits.