Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.
AuthorBenyamin, B; He, J; Zhao, Q; Gratten, J; Garton, F; Leo, PJ; Liu, Z; Mangelsdorf, M; Al-Chalabi, A; Anderson, L; ...
Source TitleNature Communications
PublisherSpringer Science and Business Media LLC
Document TypeJournal Article
CitationsBenyamin, B., He, J., Zhao, Q., Gratten, J., Garton, F., Leo, P. J., Liu, Z., Mangelsdorf, M., Al-Chalabi, A., Anderson, L., Butler, T. J., Chen, L., Chen, X. -D., Cremin, K., Deng, H. -W., Devine, M., Edson, J., Fifita, J. A., Furlong, S. ,... Fan, D. (2017). Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.. Nat Commun, 8 (1), pp.611-. https://doi.org/10.1038/s41467-017-00471-1.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606989
NHMRC Grant codeNHMRC/310667
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.
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