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Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the <jats:italic>ACSL5<\/jats:italic> locus (top SNP <jats:italic>p<\/jats:italic>\u2009=\u20092.97\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). We validated the association with <jats:italic>ACSL5<\/jats:italic> in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP <jats:italic>p<\/jats:italic>\u2009=\u20091.82\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). In the combined meta-analysis, the intronic <jats:italic>ACSL5<\/jats:italic> SNP rs3736947 showed the strongest association (<jats:italic>p<\/jats:italic>\u2009=\u20097.81\u2009\u00d7\u200910<jats:sup>\u221211<\/jats:sup>). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: <jats:italic>ERGIC1<\/jats:italic>, <jats:italic>RAPGEF5<\/jats:italic>, <jats:italic>FNBP1<\/jats:italic>, and <jats:italic>ATXN3<\/jats:italic>. These results advance our understanding of the genetic basis of sporadic ALS.<\/jats:p>","DOI":"10.1038\/s42003-020-01251-2","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T10:03:36Z","timestamp":1600855416000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral 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