Fine Mapping Analysis of the MHC Region to Identify Variants Associated With Chinese Vitiligo and SLE and Association Across These Diseases

Abstract

The important role of MHC in the pathogenesis of vitiligo and SLE has been confirmed in various populations. To map the most significant MHC variants associated with the risk of vitiligo and SLE, we conducted fine mapping analysis using 1117 vitiligo cases, 1046 SLE cases and 1693 healthy control subjects in the Han-MHC reference panel and 1000 Genomes Project phase 3. rs113465897 (P=1.03×10^-13, OR=1.64, 95%CI =1.44-1.87) and rs3129898 (P=4.21×10^-17, OR=1.93, 95%CI=1.66-2.25) were identified as being most strongly associated with vitiligo and SLE, respectively. Stepwise conditional analysis revealed additional independent signals at rs3130969(p=1.48×10^-7, OR=0.69, 95%CI=0.60-0.79), HLA-DPB1*03:01 (p=1.07×10^-6, OR=1.94, 95%CI=1.49-2.53) being linked to vitiligo and HLA-DQB1*0301 (P=4.53×10^-7, OR=0.62, 95%CI=0.52-0.75) to SLE. Considering that epidemiological studies have confirmed comorbidities of vitiligo and SLE, we used the GCTA tool to analyse the genetic correlation between these two diseases in the HLA region, the correlation coefficient was 0.79 (P=5.99×10^-10, SE=0.07), confirming their similar genetic backgrounds. Our findings highlight the value of the MHC region in vitiligo and SLE and provide a new perspective for comorbidities among autoimmune diseases.

Keywords: MHC; fine mapping; imputation; systemic lupus erythematosus; vitiligo.