Integrative Analysis of Omics Data Reveals Regulatory Network of in Vitiligo Risk.

Vitiligo is a multifactorial polygenic disorder, characterized by acquired depigmented skin and overlying hair resulting from the destruction of melanocytes. Genome-wide association studies (GWASs) of vitiligo have identified approximately 100 genetic variants. However, the identification of functional genes and their regulatory elements remains a challenge. To prioritize putative functional genes and DNAm sites, we performed a Summary data-based Mendelian Randomization (SMR) and heterogeneity in dependent instruments (HEIDI) test to integrate omics summary statistics from GWAS, expression quantitative trait locus (eQTL), and methylation quantitative trait loci (meQTL) analysis of large sample size. By integrating omics data, we identified two newly putative functional genes ( and ) associated with vitiligo and further validated by qRT-PCR in independent samples. We also identified 17 vitiligo-associated DNA methylation (DNAm) sites in Chr16, of which cg05175606 was significantly associated with the expression of and vitiligo. Colocalization analyses detected transcript of in the blood and skin colocalizing with cg05175606 at single nucleotide polymorphism (SNP) rs77651727. Our findings revealed that a shared genetic variant rs77651727 alters the cg05175606 as well as up-regulates gene expression of and further decreases the risk of vitiligo.