A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects
| Autor: | Salil A. Lachke, Pirro G. Hysi, Ronald B. Melles, Deepti Anand, Hélène Choquet, Gabriel Cuellar-Partida, Jie Yin, Thomas J. Hoffmann, Wei Wang, K. Saidas Nair, Eric Jorgenson |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Candidate gene Aging medicine.medical_treatment Science General Physics and Astronomy Genome-wide association study Locus (genetics) Biology Genome-wide association studies General Biochemistry Genetics and Molecular Biology Cataract Article Cohort Studies 03 medical and health sciences Mice 0302 clinical medicine Sex Factors Lens Crystalline medicine Animals Humans Genetic Predisposition to Disease Gene Genetics Caspase 7 Mice Knockout Molecular Epidemiology Multidisciplinary General Chemistry Cataract surgery Biobank Genetic architecture eye diseases Disease Models Animal 030104 developmental biology Logistic Models Gene Expression Regulation Ribonucleoproteins Genetic Loci Meta-analysis 030221 ophthalmology & optometry Lens diseases Genome-Wide Association Study |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. The genetic basis of cataract is not well understood. Here, the authors perform a genome-wide association multiethnic meta-analysis of cataract, finding 37 new loci and replicating known and new loci. They additionally perform sex-specific analyses, identifying new associations specific to women. |
| Databáze: | OpenAIRE |
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