In:
Communications Biology, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2020-09-23)
Abstract:
Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. 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 ACSL5 locus (top SNP p = 2.97 × 10 −8 ). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10 −4 ). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association ( p = 7.81 × 10 −11 ). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1 , RAPGEF5 , FNBP1 , and ATXN3 . These results advance our understanding of the genetic basis of sporadic ALS.
Type of Medium:
Online Resource
ISSN:
2399-3642
DOI:
10.1038/s42003-020-01251-2
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2919698-X
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