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

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 (GWA...

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Autores principales:	Fatin N. Zainul Abidin, Helena R. R. Wells, Andre Altmann, Sally J. Dawson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/fe56ffe886154576b0acee7b01f5dde9
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spelling	oai:doaj.org-article:fe56ffe886154576b0acee7b01f5dde92021-12-02T17:03:48ZHearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture10.1038/s41514-021-00069-42056-3973https://doaj.org/article/fe56ffe886154576b0acee7b01f5dde92021-07-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00069-4https://doaj.org/toc/2056-3973Abstract 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.Fatin N. Zainul AbidinHelena R. R. WellsAndre AltmannSally J. DawsonNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Fatin N. Zainul Abidin Helena R. R. Wells Andre Altmann Sally J. Dawson Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture
description	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.
format	article
author	Fatin N. Zainul Abidin Helena R. R. Wells Andre Altmann Sally J. Dawson
author_facet	Fatin N. Zainul Abidin Helena R. R. Wells Andre Altmann Sally J. Dawson
author_sort	Fatin N. Zainul Abidin
title	Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture
title_short	Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture
title_full	Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture
title_fullStr	Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture
title_full_unstemmed	Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture
title_sort	hearing difficulty is linked to alzheimer’s disease by common genetic vulnerability, not shared genetic architecture
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fe56ffe886154576b0acee7b01f5dde9
work_keys_str_mv	AT fatinnzainulabidin hearingdifficultyislinkedtoalzheimersdiseasebycommongeneticvulnerabilitynotsharedgeneticarchitecture AT helenarrwells hearingdifficultyislinkedtoalzheimersdiseasebycommongeneticvulnerabilitynotsharedgeneticarchitecture AT andrealtmann hearingdifficultyislinkedtoalzheimersdiseasebycommongeneticvulnerabilitynotsharedgeneticarchitecture AT sallyjdawson hearingdifficultyislinkedtoalzheimersdiseasebycommongeneticvulnerabilitynotsharedgeneticarchitecture
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Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture

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