Estimating the causal effect of hearing loss on Alzheimer’s disease: a Mendelian randomisation study

BackgroundHearing loss has been identified as one of the most important risk factors for Alzheimer’s disease (AD). However, the causality of this association has not been established.MethodsWe used publicly available GWAS summary statistics to construct instrumental variables for age-related hearing difficulty. We tested these genetic instruments for association with the outcome of AD using AD GWAS summary statistics in a two-sample Mendelian randomisation analysis. We used inverse-variance weighted meta-analysis to estimate the causal effect of hearing-related traits on AD, followed by secondary sensitivity analyses including a mixture of experts approach.ResultsThere was no strong evidence for a causal relationship between genetically-determined hearing difficulty (ORFE-IVW 1.27, 95% CI 0.89 to 1.82, p=0.189) and AD risk. There was no evidence to suggest that unbalanced horizontal pleiotropy was biasing the result. Power calculations indicated our instruments were sufficiently powered to detect the magnitude of effect described in case-control and cohort settings.ConclusionsOur results suggest that the size of the observed relationship between hearing loss and AD cannot be completely accounted for by a direct causal influence. Hearing loss may have more utility as a risk marker for AD than as a modifiable risk factor.