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In the following, Bayesian colocalization analysis was conducted for GWAS and protein quantitative trait loci signals to prioritize candidate genes. Differential expression analysis was then used to verify the dysregulation of risk genes in white matter and gray matter for evidence at the transcription level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 51 genes whose protein abundance had association with the MS risk were identified, of which 18 genes overlapped in the discovery and confirmation PWAS. Bayesian colocalization indicated six causal genes with genetic risk variants for the MS risk. The differential expression analysis of <jats:italic>SHMT1<\/jats:italic> (<jats:italic>P<\/jats:italic><jats:sub>FDR<\/jats:sub>\u00a0=\u00a04.82\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>)<jats:italic>, FAM120B<\/jats:italic> (<jats:italic>P<\/jats:italic><jats:sub>FDR<\/jats:sub>\u00a0=\u00a08.13\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>) in white matter and <jats:italic>ICA1L<\/jats:italic> (<jats:italic>P<\/jats:italic><jats:sub>FDR<\/jats:sub>\u00a0=\u00a03.44\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>) in gray matter confirmed the dysregulation at the transcription level. Further investigation of expression found <jats:italic>SHMT1<\/jats:italic> significantly up\u2010regulated in white matter lesion, and <jats:italic>FAM120B<\/jats:italic> up\u2010regulated in both white matter lesion and normal appearing white matter<jats:italic>. ICA1L<\/jats:italic> was down\u2010regulated in both gray matter lesion and normal appearing gray matter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Dysregulation of <jats:italic>SHMT1, FAM120B<\/jats:italic> and <jats:italic>ICA1L<\/jats:italic> may confer MS risk. Our findings shed new light on the pathogenesis of MS and prioritized promising targets for future therapy research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51699","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T08:02:02Z","timestamp":1670400122000},"page":"58-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Brain proteome\u2010wide association study linking\u2010genes in multiple sclerosis pathogenesis"],"prefix":"10.1002","volume":"10","author":[{"given":"Tingting","family":"Jia","sequence":"first","affiliation":[{"name":"Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy West China Hospital of Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni","family":"Ma","sequence":"additional","affiliation":[{"name":"Mental Health Center and Psychiatric Laboratory, the State Key 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