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Establishing a robust triangulation framework to explore the relationship between hearing loss and Parkinson's
Hao Zhang1, Keying Chen1, Tongyu Gao1
1Department of Biostatistics, School of Public Health, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China.
NPJ Parkinson'S Disease
|January 3, 2025
Summary
Hearing loss (HL) increases Parkinson
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- The association between hearing loss (HL) and Parkinson's disease (PD) is not well understood.
- Existing research suggests a potential link, but causal relationships and underlying genetic factors require further investigation.
Purpose of the Study:
- To investigate the relationship between hearing loss severity and Parkinson's disease risk.
- To explore the genetic underpinnings and potential causal links between HL and PD using multiple analytical approaches.
- To identify shared genetic loci and biological pathways connecting HL and PD.
Main Methods:
- Utilized individual-level and summary-level data from UK Biobank and large genome-wide association studies.
- Employed observational, Mendelian randomization, and genetic pleiotropy analyses.
- Performed genetic correlation and co-localization analyses to identify shared genetic influences.
Main Results:
- Increased Parkinson's disease risk was associated with greater hearing loss severity, particularly in older individuals and males.
- Hearing aid use was linked to a significant reduction in Parkinson's disease risk among males.
- While a direct causal link was not supported, genetic correlation analysis indicated a localized genetic overlap at 17q21.31.
- Identified 1545 single nucleotide polymorphisms (SNPs) and 63 genes with pleiotropic effects on both HL and PD, including novel SNPs and loci.
- These pleiotropic loci are enriched in key tissues (brain, heart, liver, pancreas) and associated with the dihydrolipoyl dehydrogenase complex pathway.
Conclusions:
- Hearing loss is associated with an increased risk of Parkinson's disease, with potential protective effects from hearing aids in males.
- Shared genetic factors contribute to the observed association, highlighting specific loci and biological pathways.
- This study provides insights into the complex interplay between hearing loss and Parkinson's disease, informing future research and potential therapeutic targets.
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