Association study and fine-mapping major histocompatibility complex analysis of pemphigus vulgaris in a Han Chinese population.

To identify possible additional genetic susceptibility loci for pemphigus vulgaris (PV), we performed a genome-wide association study (GWAS) of 240 PV cases and 1,031 controls, and we selected the top single nucleotide polymorphisms (SNPs) for replication in independent samples, with 252 cases and 1,852 controls. We identified rs11218708 (P= 3.1 × 10, OR=1.54) at 11q24.1 as significantly associated with PV. A fine-mapping analysis of PV risk in the MHC region demonstrated three independent variants predisposed to PV using stepwise analysis: HLA-DRB1*14:04 (P = 2.47 × 10;OR = 6.28), rs7454108 at the TAP2 gene (P = 2.78 × 10; OR= 3.25), and rs1051336 at the HLA-DRA gene (P= 3.06 × 10; OR = 0.33). A systematic evaluation using gene- and pathway-based analyses demonstrated a high tendency for PV susceptibility genes to be associated with autoimmunity. Our study highlighted the involvement of immune-mediated processes in the pathophysiology of PV and illustrated the value of imputation to identify variants in the MHC region.