Type 1 diabetes (T1D) is a highly heritable autoimmune disease. Although more than 50 non-HLA risk loci have been identified, the strongest associations were observed in HLA regions in Caucasian populations. The aim of this study is to identify T1D risk HLA loci in Chinese Han population and explore the risk prediction models based on these loci. A two-stage genome-wide association study (GWAS) of T1D (at least one autoantibody positive) was performed in Chinese Han population, the GWAS scan was conducted by the Illumina Human OmniZhongHua platform and included 1,045 T1D cases and 1,3controls, and the replication included 1,378 cases and 3,774 controls. Promising associations were further validated by combining with the data from the Wellcome Trust Case Control Consortium (WTCCC). Association analyses for T1D used logistic regression models assuming additive effects. Results from different stages were combined with fixed effects model in meta-analysis. In the GWAS scan stage, we identified 18 distinct genomic regions with P-values <1.00×10-5. As expected, the strongest associations with T1D were located in the HLA region, and rs1770 at MHC (OR=4.54, P<1.00×10-324), a previously identified Caucasian T1D risk locus, showed the strongest association after combining the results from different stages. Further fine mapping in the HLA region identified five independent risk loci, a novel Chinese specific locus HLA-C position 275 (P=9.78×10−12) was discovered except for rs1770, HLA-DRB1 position 11, HLA-DRB1 position74, and HLA-A position 9. Risk prediction model based on these five independent loci of HLA can achieve an AUC of 0.85 (0.84-0.87). A s the primary T1D GWA study in Asian population to date, the results identified a Chinese specific HLA locus and would be the basis of precision medicine of Chinese T1D by risk prediction based on the identified HLA loci.


K. Xu: None. Y. Chen: None. Y. Gu: None. M. Zhu: None. M. Zhang: None. M. Sun: None. X. Xu: None. H. Hsu: None. H. Chen: None. Y. Shi: None. Y. Cai: None. H. Dai: None. S. Zheng: None. X. Zheng: None. H. Zhou: None. L. Yu: None. Z. Hu: None. Z. Zhou: None. J. Weng: None. H. Shen: None. T. Yang: None.

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