763 Genome-wide association study and comprehensive HLA analysis of pemphigus

Abstract

Pemphigus is an autoimmune blistering disease, and pemphigus vulgaris (PV) and foliaceus (PF) are the two major histological subtypes. The associations of HLA molecules have been suggested, but specific HLA risk variants as well as novel risk variants outside the MHC region remain to be discovered. We performed a two-stage genome-wide association study of pemphigus in the Chinese Han population in 166 patients and 844 healthy controls with a follow-up analysis in an additional 105 patients and 996 healthy controls. Further, a comprehensive association analysis of the MHC region was performed by HLA imputation and further validation by next-generation sequencing and genotyping. Novel associations with PF were discovered SNP on 12q24.33, located within RAN and STX2 (PPF=1.57×10-9). . In addition, HLA-DRB1*14 has been demonstrated to be the primary driver of HLA association for both PV (P=1.39×10-85) and PF (P=1.69×10-19), but the association patterns of DRB1*14 alleles are different between two subtypes. Discovery of these risk loci has advanced our understanding of the genetic basis of pemphigus susceptibility, and offered opportunities for risk prediction and preventive treatment for pemphigus, in particular for PV.