| Title: | GWAS Identifies 44 Independent Associated Genomic Loci for Self-Reported Adult Hearing Difficulty in UK Biobank |
| Journal: | American Journal of Human Genetics |
| Published: | 26 Sep 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31564434/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2019.09.008 |
| URL: | https://kclpure.kcl.ac.uk/ws/files/119998969/AJHG_D_19_00186_R4_Accepted_Final_Draft.pdf |
| Citations: | 114 (40 in last 2 years) as of 8 Aug 2024 |
Publication 3084
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Abstract
Age-related hearing impairment (ARHI) is the most common sensory impairment in the aging population; a third of individuals are affected by disabling hearing loss by the age of 65. It causes social isolation and depression and has recently been identified as a risk factor for dementia. The genetic risk factors and underlying pathology of ARHI are largely unknown, meaning that targets for new therapies remain elusive, yet heritability estimates range between 35% and 55%. We performed genome-wide association studies (GWASs) for two self-reported hearing phenotypes, using more than 250,000 UK Biobank (UKBB) volunteers aged between 40 and 69 years. Forty-four independent genome-wide significant loci (p < 5E-08) were identified, considerably increasing the number of established trait loci. Thirty-four loci are novel associations with hearing loss of any form, and only one of the ten known hearing loci has a previously reported association with an ARHI-related trait. Gene sets from these loci are enriched in auditory processes such as synaptic activities, nervous system processes, inner ear morphology, and cognition, while genetic correlation analysis revealed strong positive correlations with multiple personality and psychological traits for the first time. Immunohistochemistry for protein localization in adult mouse cochlea implicate metabolic, sensory, and neuronal functions for NID2, CLRN2, and ARHGEF28. These results provide insight into the genetic landscape underlying ARHI, opening up novel therapeutic targets for further investigation. In a wider context, our study also highlights the viability of using self-report phenotypes for genetic discovery in very large samples when deep phenotyping is unavailable.</p>
15 Keywords
- Adult
- Aged
- Animals
- Biological Specimen Banks
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Hearing Disorders
- Humans
- Linkage Disequilibrium
- Mice
- Mice, Inbred C57BL
- Middle Aged
- Phenotype
- Polymorphism, Single Nucleotide
- United Kingdom
10 Authors
- Helena R R Wells
- Maxim B Freidin
- Fatin N Zainul Abidin
- Antony Payton
- Piers Dawes
- Kevin J Munro
- Cynthia C Morton
- David R Moore
- Sally J Dawson
- Frances M K Williams
1 Application
| Application ID | Title |
|---|---|
| 11516 | Understanding genetic and environmental causes of age-related hearing loss and tinnitus |
Enabling scientific discoveries that improve human health