A Gene-based Genome-wide Association Study Of Multiple Sclerosis

Background:Multiple sclerosis(MS)is considered to be an autoimmune disorder influenced by genetic and environmental factors.Many studies gave insight into the genetic determinants of multiple sclerosis(MS)through large-scale genome-wide association study(GWAS)datasets.However,further research methods of GAWS have not been developed enough to complete the heritable potential of MS.Objective: We hypothesized that the novel overlapped genes may be obtained via gene-based test in MS GWAS datasets.Methods:We analyzed a genome-wide association study(GWAS)in 9,772 subjects with multiple sclerosis cases and 17,376 healthy controls of European descent.We performed 465,434 autosomal SNPs for gene-based test by two analysis methods.We obtained two results and screened 20 significant shared gene sets(adjusted p<3.52x10-6).To discover the differential gene expressions of overlapped genes,we selected 3 samples from gene expression omnibus(GEO)series for analysis.Result:Among 14 thousands gene sets,we identified,COL11A2,DPH5,EXTL2,HLA-DOA and HLA-DOB,the 5 new significant susceptibility genes of 20 overapped ones(p<3.52x10-6).By Benjamini & Hochberg correction 8 of 20 genes had differential expressions and the GALC and HLA-DOB gene had prominent difference with nearly multiple 2 or 3.Conclusion : We report shared gene sets in MS GWAS dataset by two analytical methods,and highlight several novel MS risk variants and significant differential genes expressions.Our efforts reveal more information about hereditary characteristics of MS and also provide some basis for further studies...