1. A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis.
- Author
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Nakamura R, Misawa K, Tohnai G, Nakatochi M, Furuhashi S, Atsuta N, Hayashi N, Yokoi D, Watanabe H, Watanabe H, Katsuno M, Izumi Y, Kanai K, Hattori N, Morita M, Taniguchi A, Kano O, Oda M, Shibuya K, Kuwabara S, Suzuki N, Aoki M, Ohta Y, Yamashita T, Abe K, Hashimoto R, Aiba I, Okamoto K, Mizoguchi K, Hasegawa K, Okada Y, Ishihara T, Onodera O, Nakashima K, Kaji R, Kamatani Y, Ikegawa S, Momozawa Y, Kubo M, Ishida N, Minegishi N, Nagasaki M, and Sobue G
- Subjects
- Amyotrophic Lateral Sclerosis ethnology, Asian People genetics, Case-Control Studies, China, Coenzyme A Ligases physiology, Female, Genome-Wide Association Study, Humans, Japan, Male, Polymorphism, Single Nucleotide genetics, White People genetics, Amyotrophic Lateral Sclerosis genetics, Coenzyme A Ligases genetics, Genes genetics, Genetic Predisposition to Disease genetics
- 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.- Published
- 2020
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