Profile of Differential Promoter Activity by Nucleotide Substitution at GWAS Signals For Multiple Sclerosis

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This experimental study was conducted with completely randomized design. Genome-wide association studies (GWAS) have revealed a large number of genetic associations of nucleotide sequence variants with susceptibility to multiple sclerosis (MS). Nevertheless, studies to identify the functional relevance of these variants lag far behind identification of the GWAS signals. Expression quantitative trait loci (eQTLs) analysis and promoter activity analysis with the variants filtered by GWAS were conducted to identify their functional alleles and haplotypes. The promoter activity was assayed with reporter constructs containing variants at 8 MS GWAS signals resulted from 18 GWAS. The promoter activity differed by alternative sequence variants at upstream regions of the CYP24A1, CYP27B1, SYK, RAD21L1, PVR, ODF3B, and RGS14 genes (P