A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects

Year: 2021

Type: review

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.

Source: Nature Communications

DOI: 10.1038/s41467-021-23873-8

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

Institutions: Kaiser Permanente, Kaiser Permanente Northern California, University of Delaware, 23andMe (United States), University of California, San Francisco, University of California San Francisco Medical Center, King's College London, Great Ormond Street Hospital, University College London

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,560

Funders: U.S. Department of Health and Human Services, Ellison Medical Foundation, Robert Wood Johnson Foundation, Marin Community Foundation, Wayne and Gladys Valley Foundation, Research to Prevent Blindness, Kaiser Permanente, BrightFocus Foundation, That Man May See, National Institutes of Health, University of California, San Francisco, Medical Research Council, National Institute on Aging, National Institute of Mental Health, National Eye Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Common Fund

OpenAlex ID: W3171361629