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. 2020 Sep 25;12(1):e12108.
doi: 10.1002/dad2.12108. eCollection 2020.

Exploring the genetic relationship between hearing impairment and Alzheimer's disease

Brittany L Mitchell  1   2 , Jackson G Thorp  2   3 , David M Evans  4   5 , Dale R Nyholt  1 , Nicholas G Martin  1   2 , Michelle K Lupton  1   2
Affiliations

Exploring the genetic relationship between hearing impairment and Alzheimer's disease

Brittany L Mitchell et al. Alzheimers Dement (Amst). .

Abstract

Introduction: Hearing loss has been identified as the potentially largest modifiable risk factor for Alzheimer's disease (AD), estimated to account for a similar increase in AD risk as the apolipoprotein E (APOE) gene.

Methods: We investigated the genetic relationship between hearing loss and AD, and sought evidence for a causal relationship.

Results: We found a significant genetic overlap between hearing impairment and AD and a polygenic risk score for AD was able to significantly predict hearing loss in an independent cohort. Additionally, regions of the genome involved in inflammation were identified to be shared between hearing difficulty and AD. However, causality tests found no significant evidence of a causal relationship between these traits in either direction.

Discussion: Overall, these results show that the relationship between hearing difficulty and AD may, in part, be due to shared genes and immune response pathways between the traits. However, currently available data do not support a causal relationship.

Keywords: Alzheimer's disease; cognitive decline; dementia; genetic risk score; hearing aid; hearing loss; risk factor.

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Conflict of interest statement

All authors report no conflicts of interest in relation with this study.

Figures

FIGURE 1
FIGURE 1
A, Polygenic risk scores (PRS) for Alzheimer's disease (AD) significantly predict hearing difficulty in the PISA sample (n = 2548) at all P‐value thresholds except P < 1. * P < .01. B, Risk of self‐reported hearing loss is positively associated with AD PRS. Error bars indicate 95% confidence intervals
FIGURE 2
FIGURE 2
Left, Miami plot of single nucleotide polymorphisms in the shared MHC region (as pre‐defined by pairwise genome‐wide association study) on chromosome 6 between hearing difficulty and Alzheimer's disease (AD) indicates that the region shares causal variants. Right, Overview of genes mapped to this shared region using MAGMA; orange depicts 47 genes in this region that are significantly associated with hearing difficulty and green depicts 8 genes associated with AD. Six genes are significantly associated with both traits
FIGURE 3
FIGURE 3
No evidence for a significant causal effect between hearing difficulty and Alzheimer's disease was observed in either direction using five Mendelian randomization methods. Error bars indicate 95% confidence intervals
See this image and copyright information in PMC

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