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Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis
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-e...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606989/ https://www.ncbi.nlm.nih.gov/pubmed/28931804 http://dx.doi.org/10.1038/s41467-017-00471-1 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Benyamin, Beben |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-5606989 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-56069892017-09-22 Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis 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 Nat Commun Article 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. Nature Publishing Group UK 2017-09-20 /pmc/articles/PMC5606989/ /pubmed/28931804 http://dx.doi.org/10.1038/s41467-017-00471-1 Text en © The Author(s) 2017 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 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 Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis |
| title | Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis |
| title_full | Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis |
| title_fullStr | Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis |
| title_full_unstemmed | Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis |
| title_short | Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis |
| title_sort | cross-ethnic meta-analysis identifies association of the gpx3-tnip1 locus with amyotrophic lateral sclerosis |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606989/ https://www.ncbi.nlm.nih.gov/pubmed/28931804 http://dx.doi.org/10.1038/s41467-017-00471-1 |
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