1. Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.
- Author
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Benyamin B, He J, Zhao Q, Gratten J, Garton F, Leo PJ, Liu Z, Mangelsdorf M, Al-Chalabi A, Anderson L, Butler TJ, Chen L, Chen XD, Cremin K, Deng HW, Devine M, Edson J, Fifita JA, Furlong S, Han YY, Harris J, Henders AK, Jeffree RL, Jin ZB, Li Z, Li T, Li M, Lin Y, Liu X, Marshall M, McCann EP, Mowry BJ, Ngo ST, Pamphlett R, Ran S, Reutens DC, Rowe DB, Sachdev P, Shah S, Song S, Tan LJ, Tang L, van den Berg LH, van Rheenen W, Veldink JH, Wallace RH, Wheeler L, Williams KL, Wu J, Wu X, Yang J, Yue W, Zhang ZH, Zhang D, Noakes PG, Blair IP, Henderson RD, McCombe PA, Visscher PM, Xu H, Bartlett PF, Brown MA, Wray NR, and Fan D
- 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
- 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.- Published
- 2017
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