Age-related hearing loss was recently established as the largest modifiable risk factor for Alzheimer’s disease (AD), however, the reasons for this link remain unclear. We investigate shared underlying genetic associations using results from recent large genome-wide association studies (GWAS) on adult hearing difficulty and AD. Genetic correlation and Mendelian randomization (MR) analysis do not support a genetic correlation between the disorders, but suggest a direct causal link from AD genetic risk to hearing difficulty, driven by APOE. Systematic MR analyses on the effect of other traits revealed shared effects of glutamine, gamma-glutamylglutamine, and citrate levels on reduced risk of both hearing difficulty and AD. In addition, pathway analysis on GWAS risk variants suggests shared function in neuronal signalling pathways as well as etiology of diabetes and cardiovascular disease. However, after multiple testing corrections, neither analysis led to statistically significant associations. Altogether, our genetic-driven analysis suggests hearing difficulty and AD are linked by a shared vulnerability in molecular pathways rather than by a shared genetic architecture.

与年龄相关的听力损失最近被确定为阿尔茨海默病 (AD) 的最大可改变风险因素，然而，这种联系的原因仍不清楚。我们使用最近关于成人听力困难和 AD 的大型全基因组关联研究 (GWAS) 的结果调查共享的潜在遗传关联。遗传相关性和孟德尔随机化 (MR) 分析不支持疾病之间的遗传相关性，但表明 AD 遗传风险与听力困难之间存在直接的因果关系，由APOE驱动. 对其他性状影响的系统 MR 分析揭示了谷氨酰胺、γ-谷氨酰谷氨酰胺和柠檬酸盐水平对降低听力困难和 AD 风险的共同影响。此外，对 GWAS 风险变异的通路分析表明，神经元信号通路以及糖尿病和心血管疾病的病因具有共同的功能。然而，经过多次测试校正，两种分析都没有导致统计学上显着的关联。总而言之，我们的基因驱动分析表明，听力困难和 AD 是通过分子途径中的共同脆弱性而不是共同的遗传结构联系起来的。