PMID- 23238918 OWN - NLM STAT- MEDLINE DCOM- 20140303 LR - 20211021 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 40 IP - 3 DP - 2013 Mar TI - Genome-wide pathway analysis of a genome-wide association study on multiple sclerosis. PG - 2557-64 LID - 10.1007/s11033-012-2341-1 [doi] AB - The aims of this study were to identify candidate single nucleotide polymorphisms (SNPs) and mechanisms of multiple sclerosis (MS) and to generate SNP to gene to pathway hypotheses. A MS genome-wide association study (GWAS) dataset that included 505,763 SNPs in 500 cases and 500 controls of European descent was used in this study. Identify candidate Causal SNPs and Pathway (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 9 candidate SNPs and 5 pathways, which provided 5 hypothetical biological mechanisms. The candidate SNPs, namely, rs1802127 (MSH5), rs9277471 (human leukocyte antigen [HLA]-DPB1), rs8084 (HLA-DRA), rs7192 (HLA-DRA), rs2072895 (HLA-F), rs2735059 (HLA-F), rs915669 (HLA-G), rs915668 (HLA-G), and rs1063320 (HLA-G) were all at HLA loci (-log10(P) = 3.301-4.000). The most strongly associated pathway was rs1802127 to MSH5 to meiotic recombination and meiotic cell cycle (nominal P < 0.001, false discovery rate [FDR] < 0.001). When HLA loci were excluded, ICSNPathway analysis identified seven candidate non-HLA SNPs (rs5896 [F2], rs8181979 [SHC1], rs9297605 [TAF2], rs669 [A2 M], rs2228043 [IL6ST], rs1061622 [TNFRSF1B], rs1801516 [ATM]) and ten candidate causal pathways, which provided seven hypothetical biological mechanisms (nominal P