A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis.
A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis.
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DOI：
10.1038/s42003-020-01251-2
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发表时间：
2020-09-23
影响因子：
5.9
通讯作者：
Sobue G
中科院分区：
文献类型：
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作者：
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
肌萎缩侧索硬化症(ALS)是一种破坏性的进行性运动神经元疾病，影响所有种族的人。大约90%的ALS病例是散发性的，并被认为是由多因素引起的。为了了解散发性肌萎缩侧索硬化症的遗传学，我们对日本人群中的1,173例散发性肌萎缩侧索硬化症病例和8,925名对照进行了全基因组关联研究。对我们的日本队列和欧洲血统个体的联合荟萃分析显示，ACSL5基因座存在显著的关联(顶端SNP p = 2.97 × 10−8)。我们在对一个中国人和一个独立的日本人(1941例ALS患者，3821例对照；顶级SNP p = 1.82 × 10−4)的复制研究中验证了与ACSL5的相关性。在联合Meta分析中，内含子ACSL5SNP rs3736947的关联性最强(p = 7.81 × 10−11)。通过对完整的多种族数据集进行基于基因的分析，我们发现了与ALS显著相关的其他基因：ERGIC1、RAPGEF5、FNBP1和ATXN3。这些结果促进了我们对散发性ALS遗传基础的理解。Gen Sobue、Masao Nagaki及其同事报告了一项针对肌萎缩侧索硬化症(ALS)的全基因组关联研究，研究对象是由日本、中国和欧洲血统的人群组成的大型多民族队列。他们发现与ACSL5基因内的变异有显著关联，并使用基于基因的方法确定了与另外4个基因的新关联。
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. 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.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
5.3
作者：
Maximino JR;de Oliveira GP;Alves CJ;Chadi G
通讯作者：
Chadi G
跨种族荟萃分析确定 GPX3-TNIP1 基因座与肌萎缩侧索硬化症的关联
影响因子：
16.6
作者：
Benyamin B;He J;Zhao Q;Gratten J;Garton F;Leo PJ;Liu Z;Mangelsdorf M;Al-Chalabi A;Anderson L;Butler TJ;Chen L;Chen XD;Cremin K;Deng HW;Devine M;Edson J;Fifita JA;Furlong S;Han YY;Harris J;Henders AK;Jeffree RL;Jin ZB;Li Z;Li T;Li M;Lin Y;Liu X;Marshall M;McCann EP;Mowry BJ;Ngo ST;Pamphlett R;Ran S;Reutens DC;Rowe DB;Sachdev P;Shah S;Song S;Tan LJ;Tang L;van den Berg LH;van Rheenen W;Veldink JH;Wallace RH;Wheeler L;Williams KL;Wu J;Wu X;Yang J;Yue W;Zhang ZH;Zhang D;Noakes PG;Blair IP;Henderson RD;McCombe PA;Visscher PM;Xu H;Bartlett PF;Brown MA;Wray NR;Fan D
通讯作者：
Fan D
影响因子：
4.7
作者：
Kuriyama S;Yaegashi N;Nagami F;Arai T;Kawaguchi Y;Osumi N;Sakaida M;Suzuki Y;Nakayama K;Hashizume H;Tamiya G;Kawame H;Suzuki K;Hozawa A;Nakaya N;Kikuya M;Metoki H;Tsuji I;Fuse N;Kiyomoto H;Sugawara J;Tsuboi A;Egawa S;Ito K;Chida K;Ishii T;Tomita H;Taki Y;Minegishi N;Ishii N;Yasuda J;Igarashi K;Shimizu R;Nagasaki M;Koshiba S;Kinoshita K;Ogishima S;Takai-Igarashi T;Tominaga T;Tanabe O;Ohuchi N;Shimosegawa T;Kure S;Tanaka H;Ito S;Hitomi J;Tanno K;Nakamura M;Ogasawara K;Kobayashi S;Sakata K;Satoh M;Shimizu A;Sasaki M;Endo R;Sobue K;Tohoku Medical Megabank Project Study Group T;Yamamoto M
通讯作者：
Yamamoto M
DOI：
10.1016/j.devbrainres.2003.09.017
发表时间：
2003-12-19
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Bithell, A;Alberta, J;Williams, BP
通讯作者：
Williams, BP