| Title: | A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects |
| Journal: | Nature Communications |
| Published: | 14 Jun 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34127677/ |
| DOI: | https://doi.org/10.1038/s41467-021-23873-8 |
| URL: | https://kclpure.kcl.ac.uk/portal/en/publications/df9d491d-48e7-4705-8f04-5dc9652cea58 |
| Citations: | 52 (34 in last 2 years) as of 8 Aug 2024 |
Publication 3902
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Abstract
Cataract is the leading cause of blindness among the elderly worldwide and cataract surgery is one of the most common operations performed in the United States. As the genetic etiology of cataract formation remains unclear, we conducted a multiethnic genome-wide association meta-analysis, combining results from the GERA and UK Biobank cohorts, and tested for replication in the 23andMe research cohort. We report 54 genome-wide significant loci, 37 of which were novel. Sex-stratified analyses identified CASP7 as an additional novel locus specific to women. We show that genes within or near 80% of the cataract-associated loci are significantly expressed and/or enriched-expressed in the mouse lens across various spatiotemporal stages as per iSyTE analysis. Furthermore, iSyTE shows 32 candidate genes in the associated loci have altered gene expression in 9 different gene perturbation mouse models of lens defects/cataract, suggesting their relevance to lens biology. Our work provides further insight into the complex genetic architecture of cataract susceptibility.</p>
18 Keywords
- Aging
- Animals
- Caspase 7
- Cataract
- Cohort Studies
- Disease Models, Animal
- Gene Expression Regulation
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Lens, Crystalline
- Logistic Models
- Mice
- Mice, Knockout
- Molecular Epidemiology
- Ribonucleoproteins
- Sex Factors
11 Authors
- Hélène Choquet
- Ronald B. Melles
- Deepti Anand
- Jie Yin
- Gabriel Cuellar-Partida
- Wei Wang
- Thomas J. Hoffmann
- K. Saidas Nair
- Pirro G. Hysi
- Salil A. Lachke
- Eric Jorgenson
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