# Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults

## TL;DR

This study finds a link between cataracts and hearing difficulties in older adults and identifies shared genetic factors.

## Contribution

The study is the first to explore the epidemiologic and genetic association between cataract and hearing difficulties using large-scale data.

## Key findings

- Cataract is associated with hearing difficulties with an odds ratio of 2.12.
- Six shared genetic loci were identified between cataract and hearing difficulties.
- Candidate genes like QKI, STK17A, and TCF4 are implicated in both disorders.

## Abstract

Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98–2.27; OR, 2.03; 95% CI, 1.86–2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.

The online version contains supplementary material available at 10.1186/s40246-024-00601-z.