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Multiple sclerosis (MS) risk alleles outside the <jats:italic>major histocompatibility complex<\/jats:italic> (<jats:italic>MHC<\/jats:italic>) region were tested in NMOSD and MS genetic burden (MSGB) scores were compared between HCs and NMOSD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A SNP (rs1964995) in the <jats:italic>MHC<\/jats:italic> region was associated with NMOSD susceptibility (odds ratio (OR)\u00a0=\u00a02.33, <jats:italic>P<\/jats:italic>\u00a0=\u00a04.07\u00a0\u00d7\u00a010<jats:sup>\u221211<\/jats:sup>). <jats:italic>HLA\u2010DRB1*08:02<\/jats:italic> (OR\u00a0=\u00a02.86, <jats:italic>P<\/jats:italic>\u00a0=\u00a03.03\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>) and <jats:italic>HLA\u2010DRB1*16:02<\/jats:italic> (OR\u00a0=\u00a08.39, <jats:italic>P<\/jats:italic>\u00a0=\u00a01.92\u00a0\u00d7\u00a010<jats:sup>\u22123<\/jats:sup>) were risk alleles for NMOSD susceptibility whereas <jats:italic>HLA\u2010DRB1*09:01<\/jats:italic> was protective (OR\u00a0=\u00a00.27, <jats:italic>P<\/jats:italic>\u00a0=\u00a01.06\u00a0\u00d7\u00a010<jats:sup>\u22125<\/jats:sup>). Three MS risk variants were associated with susceptibility and MSGB scores were significantly higher in NMOSD than in HCs (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0095). A SNP in the <jats:italic>KCNMA1<\/jats:italic> (<jats:italic>potassium calcium\u2010activated channel subfamily M alpha 1<\/jats:italic>) gene was associated with disability score with genome\u2010wide significance (rs1516512, <jats:italic>P<\/jats:italic>\u00a0=\u00a02.33\u00a0\u00d7\u00a010<jats:sup>\u22128<\/jats:sup>) and transverse myelitis (OR\u00a0=\u00a01.77, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.011). KCNMA1 was immunohistochemically detected in the perivascular endfeet of astrocytes and its immunoreactivity was markedly diminished in active spinal cord lesions in NMOSD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Specific <jats:italic>HLA\u2010DRB1<\/jats:italic> alleles confer NMOSD susceptibility and <jats:italic>KCNMA1<\/jats:italic> is associated with disability and transverse myelitis in NMOSD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51147","type":"journal-article","created":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T09:16:03Z","timestamp":1601111763000},"page":"2082-2093","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Genetic factors for susceptibility to and manifestations of neuromyelitis optica"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4629-1312","authenticated-orcid":false,"given":"Takuya","family":"Matsushita","sequence":"first","affiliation":[{"name":"Department of Neurology Neurological Institute Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2516-1102","authenticated-orcid":false,"given":"Katsuhisa","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Neurology Neurological Institute Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Isobe","sequence":"additional","affiliation":[{"name":"Department of Neurological Therapeutics Graduate School of Medical Sciences Kyushu University Fukuoka 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