Benyamin Beben, He Ji, Zhao Qiongyi, Gratten Jacob, Garton Fleur, Leo Paul J, Liu Zhijun, Mangelsdorf Marie, Al-Chalabi Ammar, Anderson Lisa, Butler Timothy J, Chen Lu, Chen Xiang-Ding, Cremin Katie, Deng Hong-Weng, Devine Matthew, Edson Janette, Fifita Jennifer A, Furlong Sarah, Han Ying-Ying, Harris Jessica, Henders Anjali K, Jeffree Rosalind L, Jin Zi-Bing, Li Zhongshan, Li Ting, Li Mengmeng, Lin Yong, Liu Xiaolu, Marshall Mhairi, McCann Emily P, Mowry Bryan J, Ngo Shyuan T, Pamphlett Roger, Ran Shu, Reutens David C, Rowe Dominic B, Sachdev Perminder, Shah Sonia, Song Sharon, Tan Li-Jun, Tang Lu, van den Berg Leonard H, van Rheenen Wouter, Veldink Jan H, Wallace Robyn H, Wheeler Lawrie, Williams Kelly L, Wu Jinyu, Wu Xin, Yang Jian, Yue Weihua, Zhang Zong-Hong, Zhang Dai, Noakes Peter G, Blair Ian P, Henderson Robert D, McCombe Pamela A, Visscher Peter M, Xu Huji, Bartlett Perry F, Brown Matthew A, Wray Naomi R, Fan Dongsheng
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Nat Commun. 2017 Sep 20;8(1):611. doi: 10.1038/s41467-017-00471-1.
Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.
跨种族基因研究可以利用疾病流行病学差异和特定人群基因结构的优势。特别是，不同种族间连锁不平衡和等位基因频率模式的差异可能会提高基因定位分辨率。在此，我们在散发性肌萎缩侧索硬化症（ALS）中使用跨种族基因数据，ALS是一种成人发病、进展迅速的神经退行性疾病。我们报告了对1234例ALS病例和2850例对照的全基因组关联研究新数据的分析。我们发现跨越GPX3 - TNIP1的rs10463311与ALS存在显著关联（p = 1.3×10），并得到来自两个独立澳大利亚样本的重复支持（共576例病例和683例对照，p = 1.7×10）。GPX3和TNIP1分别与其他已知的ALS基因（SOD1和OPTN）相互作用。此外，通过基于基因的分析和基于汇总统计的孟德尔随机化分析鉴定出了GGNBP2，不过还需要进一步重复验证这一结果。我们的研究结果增进了我们对ALS遗传病因的理解。肌萎缩侧索硬化症（ALS）是一种进展迅速的神经退行性疾病。在此，雷及其同事通过跨种族荟萃分析确定了GPX3 - TNIP1基因座与ALS的关联。
