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

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23andMe Research Team, 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

Original languageEnglish
Article number3595
JournalNature Communications
Issue number1
Early online date14 Jun 2021
Accepted/In press17 May 2021
E-pub ahead of print14 Jun 2021
PublishedDec 2021

Bibliographical note

Funding Information: We are grateful to the Kaiser Permanente Northern California members who have generously agreed to participate in the Kaiser Permanente Research Program on Genes, Environment, and Health. Support for participant enrollment, survey completion, and biospecimen collection for the RPGEH was provided by the Robert Wood Johnson Foundation, the Wayne and Gladys Valley Foundation, the Ellison Medical Foundation, and Kaiser Permanente Community Benefit Programs. Genotyping of the GERA cohort was funded by a grant from the National Institute on Aging, National Institute of Mental Health, and National Institute of Health Common Fund (RC2 AG036607). H.C. and E.J. were supported by the National Eye Institute (NEI) grant R01 EY027004, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK116738 and by the National Cancer Institute (NCI) R01 CA241623. This work was also made possible in part by NIH-NEI EY002162—Core Grant for Vision Research, by the Research to Prevent Blindness Unrestricted Grant (UCSF, Ophthalmology). K.S.N. receives support from NEI grant EY022891, BrightFocus Foundation (G2019360), Marin Community Foundation-Kathlyn McPherson Masneri and Arno P. Masneri Fund, and That Man May See Inc. T.J.H. was supported by National Institutes of Aging (NIA) grant R21 AG046616. S.A.L. was supported by National Institutes of Health / National Eye Institute grants R01 EY021505 and EY029770 and D.A. was supported by a Knights Templar Pediatric Ophthalmology Career Starter Grant Award. We would like to thank the research participants and employees of 23andMe for making this work possible (see Supplementary Information for the full list of members of the 23andMe Research Team). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


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.

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