Hearing difficulty is linked to Alzheimer's disease by common genetic vulnerability, not shared genetic architecture

Fatin N Zainul Abidin; Helena R R Wells; Andre Altmann; Sally J Dawson

doi:10.1038/s41514-021-00069-4

Hearing difficulty is linked to Alzheimer's disease by common genetic vulnerability, not shared genetic architecture

NPJ Aging Mech Dis. 2021 Jul 22;7(1):17. doi: 10.1038/s41514-021-00069-4.

Authors

Fatin N Zainul Abidin^{1

2}, Helena R R Wells^{1

3}, Andre Altmann^#², Sally J Dawson^#⁴

Affiliations

¹ UCL Ear Institute, University College London, London, UK.
² Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
³ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
⁴ UCL Ear Institute, University College London, London, UK. sally.dawson@ucl.ac.uk.

^# Contributed equally.

Abstract

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.

Abstract

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