# The Role of Genetic and Non-Genetic Factors and Causal Mechanisms Underlying Cataract Susceptibility For Risk Prediction

> **NIH NIH R01** · KAISER FOUNDATION RESEARCH INSTITUTE · 2024 · $404,695

## Abstract

Abstract
Age-related cataract, defined as ocular lens opacity, is a leading cause of blindness worldwide. Cataract is also
associated with injurious falls and increased mortality and is a significant public health problem in the U.S.,
accounting for approximately 60% of Medicare costs related to vision. Given the aging U.S. population, cataract
surgery demand is expected to double over the next 25 years. Thus, it is important to understand the etiology of
cataract to identify at-risk patients and develop effective prevention strategies. Recently, we conducted a large-
scale multiethnic genome-wide association study (GWAS) meta-analysis of cataract that has identified 55
genetic loci, including 38 novel loci, that underlie the risk of cataract. Majority of the genes in these loci were
independently supported as promising candidates for cataract by the database iSyTE (integrated Systems Tool
for Eye gene discovery), based on their significant expression in the lens. While these data uncovered potential
new causal genes in the identified loci, their function in the lens is not defined and their role underlying cataract
risk remains largely unknown. Further, whether cataract-loci regulate genes and how regulation differs across
tissues has not yet been explored. Our study also identified strong genetic correlations between cataract and
several disorders/traits, including, glaucoma, myopia, cigarettes smoking, and BMI, supporting previous
observational studies. However, it is not clear that these associations are causal. Finally, no predictive tool exists
for evaluating individuals at-risk for cataract. The overall objective of this proposal is to understand the role
of genetic and non-genetic factors and causal mechanisms underlying the etiology of cataract and develop a
prediction tool to facilitate risk-stratified screening for cataract. By leveraging a rich multiethnic cohort, with both
genome-wide genotype data and extensive clinical data collected through electronic health records, and using
whole-exome sequencing (WES) data of UK Biobank participants, we will accomplish the following specific
aims: 1.a) Identify novel genetic predictors of cataract risk using high quality WES data and transcriptome-wide
association study (TWAS) approach; 1.b) Evaluate whether glaucoma, myopic refractive error, diabetes, high
blood pressure, high BMI, cigarette smoking, or alcohol consumption and other clinical and behavioral factors
are causal risk factors of cataract using a Mendelian randomization approach; 2) Develop risk prediction models
of cataract risk by integrating polygenic risk scores along with other risk factors; and 3) Determine the function –
in the lens using animal models – of novel candidate genes prioritized in cataract-associated loci. This proposed
research is significant because it will fill an important gap in cataract genetics and will provide important
mechanistic insights into the pathogenesis of cataract. The project is innovative in ...

## Key facts

- **NIH application ID:** 10875664
- **Project number:** 5R01EY033010-03
- **Recipient organization:** KAISER FOUNDATION RESEARCH INSTITUTE
- **Principal Investigator:** Helene Choquet
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $404,695
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875664

## Citation

> US National Institutes of Health, RePORTER application 10875664, The Role of Genetic and Non-Genetic Factors and Causal Mechanisms Underlying Cataract Susceptibility For Risk Prediction (5R01EY033010-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10875664. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*