An Exploration of HLA Variants associated with Type-1 Diabetes Progression

Thesis (Master's)--University of Washington, 2021The Diabetes Prevention Trial-1(DPT-1) assembled genome sequences on 711 participants with the goal of identifying HLA variants associated with Type 1 Diabetes(T1D) progression. We assessed HLA alleles and haplotypes across 9 distinct HLA genes for correlation between time of patient seroconversion to clinically diagnosed T1D. Using a Cox proportional hazards regression model for each approach, we performed an allelic association analysis across 302 HLA alleles and ran a haplotype association analysis across all possible gene pairs within the study. The results identified one allele, DQB1*03:02:01, and the three following haplotypes as significantly associated with T1D progression :DQA1*03:01:01-DQB1*03:02:01, DQA1*03:01:01-B*18:01:01, and DQA1*03:01:01-B*35:01:01. Our results support prior significant findings within T1D literature regarding the association of the identified HLA variants within our study and the risk for developing T1D