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Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.
- Source :
-
Nature communications [Nat Commun] 2017 Sep 20; Vol. 8 (1), pp. 611. Date of Electronic Publication: 2017 Sep 20. - Publication Year :
- 2017
-
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 <superscript>-8</superscript> ), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10 <superscript>-3</superscript> ). 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.
- Subjects :
- Amyotrophic Lateral Sclerosis ethnology
Australia
China
Genome-Wide Association Study
High-Throughput Nucleotide Sequencing
Humans
Sequence Analysis, DNA
Amyotrophic Lateral Sclerosis genetics
Asian People genetics
DNA-Binding Proteins genetics
Glutathione Peroxidase genetics
White People genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 28931804
- Full Text :
- https://doi.org/10.1038/s41467-017-00471-1