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A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis
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 associatio...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511394/ https://www.ncbi.nlm.nih.gov/pubmed/32968195 http://dx.doi.org/10.1038/s42003-020-01251-2 |
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| author | Nakamura, Ryoichi Misawa, Kazuharu Tohnai, Genki Nakatochi, Masahiro Furuhashi, Sho Atsuta, Naoki Hayashi, Naoki Yokoi, Daichi Watanabe, Hazuki Watanabe, Hirohisa Katsuno, Masahisa Izumi, Yuishin Kanai, Kazuaki Hattori, Nobutaka Morita, Mitsuya Taniguchi, Akira Kano, Osamu Oda, Masaya Shibuya, Kazumoto Kuwabara, Satoshi Suzuki, Naoki Aoki, Masashi Ohta, Yasuyuki Yamashita, Toru Abe, Koji Hashimoto, Rina Aiba, Ikuko Okamoto, Koichi Mizoguchi, Kouichi Hasegawa, Kazuko Okada, Yohei Ishihara, Tomohiko Onodera, Osamu Nakashima, Kenji Kaji, Ryuji Kamatani, Yoichiro Ikegawa, Shiro Momozawa, Yukihide Kubo, Michiaki Ishida, Noriko Minegishi, Naoko Nagasaki, Masao Sobue, Gen |
| author_facet | Nakamura, Ryoichi Misawa, Kazuharu Tohnai, Genki Nakatochi, Masahiro Furuhashi, Sho Atsuta, Naoki Hayashi, Naoki Yokoi, Daichi Watanabe, Hazuki Watanabe, Hirohisa Katsuno, Masahisa Izumi, Yuishin Kanai, Kazuaki Hattori, Nobutaka Morita, Mitsuya Taniguchi, Akira Kano, Osamu Oda, Masaya Shibuya, Kazumoto Kuwabara, Satoshi Suzuki, Naoki Aoki, Masashi Ohta, Yasuyuki Yamashita, Toru Abe, Koji Hashimoto, Rina Aiba, Ikuko Okamoto, Koichi Mizoguchi, Kouichi Hasegawa, Kazuko Okada, Yohei Ishihara, Tomohiko Onodera, Osamu Nakashima, Kenji Kaji, Ryuji Kamatani, Yoichiro Ikegawa, Shiro Momozawa, Yukihide Kubo, Michiaki Ishida, Noriko Minegishi, Naoko Nagasaki, Masao Sobue, Gen |
| author_sort | Nakamura, Ryoichi |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-7511394 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-75113942020-10-08 A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis Nakamura, Ryoichi Misawa, Kazuharu Tohnai, Genki Nakatochi, Masahiro Furuhashi, Sho Atsuta, Naoki Hayashi, Naoki Yokoi, Daichi Watanabe, Hazuki Watanabe, Hirohisa Katsuno, Masahisa Izumi, Yuishin Kanai, Kazuaki Hattori, Nobutaka Morita, Mitsuya Taniguchi, Akira Kano, Osamu Oda, Masaya Shibuya, Kazumoto Kuwabara, Satoshi Suzuki, Naoki Aoki, Masashi Ohta, Yasuyuki Yamashita, Toru Abe, Koji Hashimoto, Rina Aiba, Ikuko Okamoto, Koichi Mizoguchi, Kouichi Hasegawa, Kazuko Okada, Yohei Ishihara, Tomohiko Onodera, Osamu Nakashima, Kenji Kaji, Ryuji Kamatani, Yoichiro Ikegawa, Shiro Momozawa, Yukihide Kubo, Michiaki Ishida, Noriko Minegishi, Naoko Nagasaki, Masao Sobue, Gen Commun Biol Article 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. Nature Publishing Group UK 2020-09-23 /pmc/articles/PMC7511394/ /pubmed/32968195 http://dx.doi.org/10.1038/s42003-020-01251-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Nakamura, Ryoichi Misawa, Kazuharu Tohnai, Genki Nakatochi, Masahiro Furuhashi, Sho Atsuta, Naoki Hayashi, Naoki Yokoi, Daichi Watanabe, Hazuki Watanabe, Hirohisa Katsuno, Masahisa Izumi, Yuishin Kanai, Kazuaki Hattori, Nobutaka Morita, Mitsuya Taniguchi, Akira Kano, Osamu Oda, Masaya Shibuya, Kazumoto Kuwabara, Satoshi Suzuki, Naoki Aoki, Masashi Ohta, Yasuyuki Yamashita, Toru Abe, Koji Hashimoto, Rina Aiba, Ikuko Okamoto, Koichi Mizoguchi, Kouichi Hasegawa, Kazuko Okada, Yohei Ishihara, Tomohiko Onodera, Osamu Nakashima, Kenji Kaji, Ryuji Kamatani, Yoichiro Ikegawa, Shiro Momozawa, Yukihide Kubo, Michiaki Ishida, Noriko Minegishi, Naoko Nagasaki, Masao Sobue, Gen A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis |
| title | A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis |
| title_full | A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis |
| title_fullStr | A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis |
| title_full_unstemmed | A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis |
| title_short | A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis |
| title_sort | multi-ethnic meta-analysis identifies novel genes, including acsl5, associated with amyotrophic lateral sclerosis |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511394/ https://www.ncbi.nlm.nih.gov/pubmed/32968195 http://dx.doi.org/10.1038/s42003-020-01251-2 |
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