A Yale-led study aimed to investigate the reasons why certain adults develop hearing problems. The study sought to shed light on the underlying factors contributing to adult hearing issues by researching this topic.
While rare mutations in childhood usually cause congenital hearing impairment, hearing problems in adults are believed to be influenced by a combination of polygenic risk and environmental factors. Although genome-wide association studies have identified several risk genes associated with adult hearing problems, large-scale genetic studies have not thoroughly examined some factors. For instance, there is limited understanding of why hearing problems are more prevalent, severe, and earlier onset in men than women and how hearing-related polygenic risk manifests in individuals from diverse ancestral backgrounds.
The molecular mechanisms underlying the association between environmental risk factors and hearing problems remain unclear. However, a recent collaborative study involving researchers from Yale, Harvard University, and the University of California San Diego has made significant progress in understanding the predisposition to age-related hearing issues.
To thoroughly investigate hearing problems (HP), scientists utilized multiple large-scale datasets, including the UK Biobank, Nurses’ Health Studies (I and II), Health Professionals Follow-up Study, and the Million Veteran Program. The study involved 748,668 adult participants, with a discovery group of 501,825 individuals, a replication group of 226,043 individuals, and a cross-ancestry replication group of 20,800 individuals.
The researchers identified 54 risk variants, including 12 novel variants, that may contribute to hearing problems. They also discovered that hormonal regulation could affect the differences observed between hearing problems in men and women.
Furthermore, the study examined multiple ancestry groups and found that the polygenic risk associated with hearing problems is shared among different human populations. The researchers also observed that genes involved in brain development interact with sex, noise pollution, and tobacco smoking, affecting their association with hearing problems.
Our results support that large-scale genetic studies are useful instruments to understand the biology and the epidemiology of hearing problems in adults,” said Renato Polimanti, Ph.D., associate professor of psychiatry at Yale School of Medicine and senior author of the study.
The study’s findings, published in Genome Medicine, have important implications for drug development and identifying at-risk older adults who may experience hearing loss. The research can potentially influence how hearing problems in older adults are assessed and treated. Since hearing loss can lead to social isolation and have significant health, psychosocial, and economic consequences, the study’s outcomes can potentially enhance the quality of life for those affected.
The study’s findings offer valuable insights into the biology and epidemiology of hearing problems (HP) in adults. The sex-specific analyses and transcriptomic associations reveal potential molecular pathways that could be targeted for drug development or repurposing. The identified causal relationships may also inform the development of preventive screening programs to identify individuals at risk of HP.
Journal Reference:
- De Angelis, F., Zeleznik, O.A., Wendt, F.R. et al. Sex differences in the polygenic architecture of hearing problems in adults. Genome Med 15, 36 (2023). DOI: 10.1186/s13073-023-01186-3