Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.
Beben BenyaminJi HeQiong-Yi ZhaoJacob GrattenFleur GartonPaul J LeoZhijun LiuMarie MangelsdorfAmmar Al ChalabiLisa AndersonTimothy J ButlerLu ChenXiang-Ding ChenKatie CreminHong-Weng DengMatthew DevineJanette EdsonJennifer A FifitaSarah FurlongYing-Ying HanJessica HarrisAnjali K HendersRosalind L JeffreeZi-Bing JinZhongshan LiTing LiMengmeng LiYong LinXiaolu LiuMhairi MarshallEmily P McCannBryan J MowryShyuan T NgoRoger PamphlettShu RanDavid C ReutensDominic B RowePerminder Singh SachdevSonia ShahSharon SongLi-Jun TanLu TangLeonard H van den BergWouter van RheenenJan H VeldinkRobyn H WallaceLawrie WheelerKelly Louise WilliamsJinyu WuXin WuJian YangWeihua YueZong-Hong ZhangDai ZhangPeter G NoakesIan P BlairRobert D HendersonPamela A McCombePeter M VisscherHuji XuPerry F BartlettMatthew A BrownNaomi R WrayDongsheng FanPublished in: Nature communications (2017)
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.
Keyphrases
- amyotrophic lateral sclerosis
- genome wide
- copy number
- meta analyses
- systematic review
- genome wide association study
- dna methylation
- randomized controlled trial
- electronic health record
- big data
- high resolution
- single molecule
- risk factors
- gene expression
- transcription factor
- deep learning
- hepatitis c virus
- late onset
- human immunodeficiency virus
- artificial intelligence