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.

中文翻译：

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中老年人白内障与听力困难之间的流行病学关联和共同遗传结构

年龄相关性白内障和听力困难是全球老年人中经常共存的主要感觉障碍，对生活质量产生切实影响。然而，白内障和听力困难之间的流行病学关联仍未被探索，而对于两者是否具有相同的遗传病因知之甚少。我们首先使用覆盖 502,543 人的英国生物库调查了白内障和听力困难之间的临床关联。进行了非匹配分析（针对混杂因素进行调整）和匹配分析（根据混杂因素为每位白内障患者匹配一个对照），并证实白内障与听力困难相关（OR，2.12；95% CI，1.98-2.27； OR，2.03；95% CI，1.86-2.23）。此外，我们基于最大的白内障全基因组关联研究，使用双变量因果混合模型（MiXeR）和条件/结合错误发现率方法，在常见变异水平上探索和量化了这两种复杂感觉障碍的共享遗传结构（N = 585,243）和听力困难（N = 323,978）。尽管仅检测到可忽略不计的遗传相关性，但我们观察到白内障和听力困难之间的多基因重叠，并确定了 6 个具有混合方向影响的共享基因座。对共享基因座的后续分析表明候选基因 QKI、STK17A、TYR、NSF 和 TCF4 可能与白内障和听力困难的病理生理学有关。总之，这项研究证明了白内障和听力困难之间存在流行病学关联，并为这两种疾病在共同变异水平上的共同遗传结构提供了新的见解。