A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

被引：46

作者：

Nakamura, Ryoichi ^{[1
]}

Misawa, Kazuharu ^{[2
,3
]}

Tohnai, Genki ^{[1
]}

Nakatochi, Masahiro ^{[4
]}

Furuhashi, Sho ^{[2
]}

Atsuta, Naoki ^{[1
]}

Hayashi, Naoki ^{[1
]}

Yokoi, Daichi ^{[1
,5
]}

Watanabe, Hazuki ^{[1
,6
]}

Watanabe, Hirohisa ^{[7
,8
]}

Katsuno, Masahisa ^{[1
]}

Izumi, Yuishin ^{[9
]}

Kanai, Kazuaki ^{[10
,11
]}

Hattori, Nobutaka ^{[10
]}

Morita, Mitsuya ^{[12
]}

Taniguchi, Akira ^{[13
]}

Kano, Osamu ^{[14
]}

Oda, Masaya ^{[15
]}

Shibuya, Kazumoto ^{[16
]}

Kuwabara, Satoshi ^{[16
]}

Suzuki, Naoki ^{[17
]}

Aoki, Masashi ^{[17
]}

Ohta, Yasuyuki ^{[18
]}

Yamashita, Toru ^{[18
]}

Abe, Koji ^{[18
]}

Hashimoto, Rina ^{[19
]}

Aiba, Ikuko ^{[19
]}

Okamoto, Koichi ^{[20
]}

Mizoguchi, Kouichi ^{[21
]}

Hasegawa, Kazuko ^{[22
]}

Okada, Yohei ^{[23
]}

Ishihara, Tomohiko ^{[24
]}

Onodera, Osamu ^{[24
]}

Nakashima, Kenji ^{[25
]}

Kaji, Ryuji ^{[9
]}

Kamatani, Yoichiro ^{[26
]}

Ikegawa, Shiro ^{[27
]}

Momozawa, Yukihide ^{[28
]}

Kubo, Michiaki ^{[29
]}

Ishida, Noriko ^{[2
]}

Minegishi, Naoko ^{[2
]}

Nagasaki, Masao ^{[2
,30
,31
]}

Sobue, Gen ^{[1
,7
,32
]}

机构：

[1] Nagoya Univ, Dept Neurol, Grad Sch Med, Nagoya, Aichi, Japan

[2] Tohoku Univ, Tohoku Med Megabank Org, Sendai, Miyagi, Japan

[3] Kansai Med Univ, Inst Biomed Sci, Dept Mol Genome Anal, Hirakata, Osaka, Japan

[4] Nagoya Univ, Dept Nursing, Div Data Sci, Grad Sch Med, Nagoya, Aichi, Japan

[5] Kakeyu Hosp, Dept Neurol, Kakeyu Misayama Rehabil Ctr, Ueda, Nagano, Japan

[6] Japanese Red Cross Nagoya Daiichi Hosp, Dept Neurol, Nagoya, Aichi, Japan

[7] Nagoya Univ, Brain & Mind Res Ctr, Nagoya, Aichi, Japan

[8] Fujita Hlth Univ, Dept Neurol, Toyoake, Aichi, Japan

[9] Tokushima Univ, Inst Biomed Sci, Dept Neurol, Grad Sch, Tokushima, Japan

[10] Juntendo Univ, Dept Neurol, Grad Sch Med, Tokyo, Japan

[11] Fukushima Med Univ, Dept Neurol, Sch Med, Fukushima, Japan

[12] Jichi Med Univ, Dept Internal Med, Div Neurol, Shimotsuke, Tochigi, Japan

[13] Mie Univ, Dept Neurol, Grad Sch Med, Tsu, Mie, Japan

[14] Toho Univ, Dept Internal Med, Div Neurol, Fac Med, Tokyo, Japan

[15] Vihara Hananosato Hosp, Dept Neurol, Miyoshi, Hiroshima, Japan

[16] Chiba Univ, Grad Sch Med, Dept Neurol, Chiba, Japan

[17] Tohoku Univ, Dept Neurol, Sch Med, Sendai, Miyagi, Japan

[18] Okayama Univ, Dept Neurol, Grad Sch Med, Okayama, Japan

[19] Natl Hosp Org, Dept Neurol, Higashinagoya Natl Hosp, Nagoya, Aichi, Japan

[20] Geriatr Res Inst & Hosp, Dept Neurol, Maebashi, Gunma, Japan

[21] Natl Hosp Org, Dept Neurol, Shizuoka Med Ctr, Shizuoka, Japan

[22] Natl Hosp Org, Sagamihara Natl Hosp, Div Neurol, Sagamihara, Kanagawa, Japan

[23] Aichi Med Univ, Dept Neurol, Nagakute, Aichi, Japan

[24] Niigata Univ, Brain Res Inst, Dept Neurol, Niigata, Japan

[25] Natl Hosp Org, Matsue Med Ctr, Dept Neurol, Matsue, Shimane, Japan

[26] RIKEN, Lab Stat & Translat Genet, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[27] RIKEN, Lab Bone & Joint Dis, Ctr Integrat Med Sci, Tokyo, Japan

[28] RIKEN, Lab Genotyping Dev, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[29] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[30] Kyoto Univ, Ctr Promot Interdisciplinary Educ & Res, Sakyo Ku, Kyoto, Japan

[31] Kyoto Univ, Ctr Genom Med, Grad Sch Med, Sakyo Ku, Kyoto, Japan

[32] Aichi Med Univ, Nagakute, Aichi, Japan

来源：

COMMUNICATIONS BIOLOGY | 2020年 / 3卷 / 01期

基金：

日本学术振兴会;

关键词：

GENOME-WIDE ASSOCIATION; FOLLOW-UP; MR-GEF; EXPRESSION; RISK; SUSCEPTIBILITY; EXPANSIONS; VARIANTS; PROJECT; PROTEIN;

D O I：

10.1038/s42003-020-01251-2

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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=2.97x10(-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=1.82x10(-4)). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p=7.81x10(-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. Gen Sobue, Masao Nagasaki and colleagues report a genome-wide association study for amyotrophic lateral sclerosis (ALS) in a large, multi-ethnic cohort comprising Japanese, Chinese, and European ancestry populations. They find a significant association to variants within the ACSL5 gene and identify novel associations with 4 additional genes using a gene-based approach.

引用

页数：9

共 51 条

[11] MAGMA: Generalized Gene-Set Analysis of GWAS Data [J].

de Leeuw, Christiaan A. ;

Mooij, Joris M. ;

Heskes, Tom ;

Posthuma, Danielle .

PLOS COMPUTATIONAL BIOLOGY, 2015, 11 (04)

[12] Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS [J].

Elden, Andrew C. ;

Kim, Hyung-Jun ;

Hart, Michael P. ;

Chen-Plotkin, Alice S. ;

Johnson, Brian S. ;

Fang, Xiaodong ;

Armakola, Maria ;

Geser, Felix ;

Greene, Robert ;

Lu, Min Min ;

Padmanabhan, Arun ;

Clay-Falcone, Dana ;

McCluskey, Leo ;

Elman, Lauren ;

Juhr, Denise ;

Gruber, Peter J. ;

Rueb, Udo ;

Auburger, Georg ;

Trojanowski, John Q. ;

Lee, Virginia M. -Y. ;

Van Deerlin, Vivianna M. ;

Bonini, Nancy M. ;

Gitler, Aaron D. .

NATURE, 2010, 466 (7310) :1069-U77

[13]

Ellingson Sally R, 2016, F1000Res, V5, P1889, DOI 10.12688/f1000research.9271.1

[14] Ataxin-3 Protein and RNA Toxicity in Spinocerebellar Ataxia Type 3: Current Insights and Emerging Therapeutic Strategies [J].

Evers, Melvin M. ;

Toonen, Lodewijk J. A. ;

van Roon-Mom, Willeke M. C. .

MOLECULAR NEUROBIOLOGY, 2014, 49 (03) :1513-1531

[15]

Gagliardi Stella, 2018, Noncoding RNA Res, V3, P226, DOI 10.1016/j.ncrna.2018.11.004

[16] Prognosis of amyotrophic lateral sclerosis patients undergoing tracheostomy invasive ventilation therapy in Japan [J].

Hayashi, Naoki ;

Atsuta, Naoki ;

Yokoi, Daichi ;

Nakamura, Ryoichi ;

Nakatochi, Masahiro ;

Katsuno, Masahisa ;

Izumi, Yuishin ;

Kanai, Kazuaki ;

Hattori, Nobutaka ;

Taniguchi, Akira ;

Morita, Mitsuya ;

Kano, Osamu ;

Shibuya, Kazumoto ;

Kuwabara, Satoshi ;

Suzuki, Naoki ;

Aoki, Masashi ;

Aiba, Ikuko ;

Mizoguchi, Kouichi ;

Oda, Masaya ;

Kaji, Ryuji ;

Sobue, Gen .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2020, 91 (03) :285-290

[17] Overview of BioBank Japan follow-up data in 32 diseases [J].

Hirata, Makoto ;

Nagai, Akiko ;

Kamatani, Yoichiro ;

Ninomiya, Toshiharu ;

Tamakoshi, Akiko ;

Yamagata, Zentaro ;

Kubo, Michiaki ;

Muto, Kaori ;

Kiyohara, Yutaka ;

Mushiroda, Taisei ;

Murakami, Yoshinori ;

Yuji, Koichiro ;

Furukawa, Yoichi ;

Zembutsu, Hitoshi ;

Tanaka, Toshihiro ;

Ohnishi, Yozo ;

Nakamura, Yusuke ;

Matsuda, Koichi .

JOURNAL OF EPIDEMIOLOGY, 2017, 27 (03) :S22-S28

[18] Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study [J].

Hozawa, Atsushi ;

Tanno, Kozo ;

Nakaya, Naoki ;

Nakamura, Tomohiro ;

Tsuchiya, Naho ;

Hirata, Takumi ;

Narita, Akira ;

Kogure, Mana ;

Nochioka, Kotaro ;

Sasaki, Ryohei ;

Takanashi, Nobuyuki ;

Otsuka, Kotaro ;

Sakata, Kiyomi ;

Kuriyama, Shinichi ;

Kikuya, Masahiro ;

Tanabe, Osamu ;

Sugawara, Junichi ;

Suzuki, Kichiya ;

Suzuki, Yoichi ;

Kodama, Eiichi N. ;

Fuse, Nobuo ;

Kiyomoto, Hideyasu ;

Tomita, Hiroaki ;

Uruno, Akira ;

Hamanaka, Yohei ;

Metoki, Hirohito ;

Ishikuro, Mami ;

Obara, Taku ;

Kobayashi, Tomoko ;

Kitatani, Kazuyuki ;

Takai-Igarashi, Takako ;

Ogishima, Soichi ;

Satoh, Mamoru ;

Ohmomo, Hideki ;

Tsuboi, Akito ;

Egawa, Shinichi ;

Ishii, Tadashi ;

Ito, Kiyoshi ;

Ito, Sadayoshi ;

Taki, Yasuyuki ;

Minegishi, Naoko ;

Ishii, Naoto ;

Nagasaki, Masao ;

Igarashi, Kazuhiko ;

Koshiba, Seizo ;

Shimizu, Ritsuko ;

Tamiya, Gen ;

Nakayama, Keiko ;

Motohashi, Hozumi ;

Yasuda, Jun .

JOURNAL OF EPIDEMIOLOGY, 2021, 31 (01) :65-76

[19] Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases [J].

Kanai, Masahiro ;

Akiyama, Masato ;

Takahashi, Atsushi ;

Matoba, Nana ;

Momozawa, Yukihide ;

Ikeda, Masashi ;

Iwata, Nakao ;

Ikegawa, Shiro ;

Hirata, Makoto ;

Matsuda, Koichi ;

Kubo, Michiaki ;

Okada, Yukinori ;

Kamatani, Yoichiro .

NATURE GENETICS, 2018, 50 (03) :390-+

[20] Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum [J].

Karch, Celeste M. ;

Wen, Natalie ;

Fan, Chun C. ;

Yokoyama, Jennifer S. ;

Kouri, Naomi ;

Ross, Owen A. ;

Hoeglinger, Gunter ;

Mueller, Ulrich ;

Ferrari, Raffaele ;

Hardy, John ;

Schellenberg, Gerard D. ;

Sleiman, Patrick M. ;

Momeni, Parastoo ;

Hess, Christopher P. ;

Miller, Bruce L. ;

Sharma, Manu ;

Van Deerlin, Vivianna ;

Smeland, Olav B. ;

Andreassen, Ole A. ;

Dale, Anders M. ;

Desikan, Rahul S. .

JAMA NEUROLOGY, 2018, 75 (07) :860-875

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