Suggestive genetic association between age-related biomarkers and hearing impairment: a mendelian randomization study
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Xiaojun Jiang1, Chen Tang2, Wei Yuan3
1Chongqing Medical University, Department of Otolaryngology, Chongqing, China; Chongqing University, School of Medicine, Renji Hospital, Department of Otolaryngology, Chongqing, China; The Fifth People's Hospital of Chongqing, Chongqing, China.
Objective:
Observational studies suggest links between biological aging biomarkers and hearing impairment, but causal inference remains limited. Mendelian Randomization (MR) offers a genetic epidemiological approach to explore potential causal relationships. We used MR to evaluate potential causal associations between various aging biomarkers and five subtypes of hearing impairment.
Methods:
We conducted a two-sample MR study using summary data from large-scale, European-ancestry genome-wide association studies. Biological aging biomarkers, including epigenetic clocks, overall and cell-specific telomere length, were used as exposures. Outcomes were age-related hearing impairment and four other subtypes. The inverse variance weighted method was our primary analysis, supported by comprehensive sensitivity analyses to assess result stability.
Results:
Our analysis observed nominal associations related to immune cell subtypes. Genetically predicted longer granulocyte telomere length was nominally associated with lower odds of mixed hearing loss (OR = 0.84, 95% CI 0.74‒0.96, p = 0.009), whereas longer leukocyte telomere length was nominally associated with higher odds of mixed hearing loss (OR = 1.21, 95% CI: 1.03-1.42, p = 0.02). Furthermore, a higher proportion of granulocytes was nominally associated with lower odds of age-related hearing impairment (OR = 0.72, 95% CI: 0.55‒0.95, p = 0.02). Although sensitivity analyses did not indicate substantial heterogeneity and horizontal pleiotropy, these associations should be interpreted with caution due to the lack of robust FDR-corrected evidence.
Conclusion:
Our findings suggest a complex landscape of cell-type specific and paradoxical associations. This may help shift attention from general anti-aging interventions towards dissecting specific cellular pathways for hearing health.
Level Of Evidence:
This two-sample Mendelian randomization study provides genetic evidence suggesting potential associations between age-related biomarkers and hearing impairment, complementing findings from conventional observational studies.
