Title |
Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis
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Published in |
Nature Communications, September 2017
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DOI | 10.1038/s41467-017-00471-1 |
Pubmed ID | |
Authors |
Beben Benyamin, Ji He, Qiongyi Zhao, Jacob Gratten, Fleur Garton, Paul J. Leo, Zhijun Liu, Marie Mangelsdorf, Ammar Al-Chalabi, Lisa Anderson, Timothy J. Butler, Lu Chen, Xiang-Ding Chen, Katie Cremin, Hong-Weng Deng, Matthew Devine, Janette Edson, Jennifer A. Fifita, Sarah Furlong, Ying-Ying Han, Jessica Harris, Anjali K. Henders, Rosalind L. Jeffree, Zi-Bing Jin, Zhongshan Li, Ting Li, Mengmeng Li, Yong Lin, Xiaolu Liu, Mhairi Marshall, Emily P. McCann, Bryan J. Mowry, Shyuan T. Ngo, Roger Pamphlett, Shu Ran, David C. Reutens, Dominic B. Rowe, Perminder Sachdev, Sonia Shah, Sharon Song, Li-Jun Tan, Lu Tang, Leonard H. van den Berg, Wouter van Rheenen, Jan H. Veldink, Robyn H. Wallace, Lawrie Wheeler, Kelly L. Williams, Jinyu Wu, Xin Wu, Jian Yang, Weihua Yue, Zong-Hong Zhang, Dai Zhang, Peter G. Noakes, Ian P. Blair, Robert D. Henderson, Pamela A. McCombe, Peter M. Visscher, Huji Xu, Perry F. Bartlett, Matthew A. Brown, Naomi R. Wray, Dongsheng Fan |
Abstract |
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(-8)), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10(-3)). 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Australia | 4 | 18% |
United States | 4 | 18% |
Netherlands | 1 | 5% |
United Kingdom | 1 | 5% |
Sweden | 1 | 5% |
Germany | 1 | 5% |
Unknown | 10 | 45% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 15 | 68% |
Scientists | 7 | 32% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 119 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 22 | 18% |
Student > Master | 16 | 13% |
Student > Bachelor | 14 | 12% |
Student > Ph. D. Student | 11 | 9% |
Professor | 10 | 8% |
Other | 17 | 14% |
Unknown | 29 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 28 | 24% |
Medicine and Dentistry | 16 | 13% |
Neuroscience | 15 | 13% |
Agricultural and Biological Sciences | 13 | 11% |
Nursing and Health Professions | 3 | 3% |
Other | 11 | 9% |
Unknown | 33 | 28% |