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., Sobue, G.
Communications Biology 3(1) 2020年
<title>Abstract</title>
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 <italic>ACSL5</italic> locus (top SNP <italic>p</italic> = 2.97 × 10−8). We validated the association with <italic>ACSL5</italic> in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP <italic>p</italic> = 1.82 × 10−4). In the combined meta-analysis, the intronic <italic>ACSL5</italic> SNP rs3736947 showed the strongest association (<italic>p</italic> = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: <italic>ERGIC1</italic>, <italic>RAPGEF5</italic>, <italic>FNBP1</italic>, and <italic>ATXN3</italic>. These results advance our understanding of the genetic basis of sporadic ALS.