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Sex differences, cross-ancestry generalizability, and noise-smoking interactions in the polygenic architecture of hearing loss in adults

Year: 2022
Type: preprint
Study design: Observational Study
Abstract: We conducted a comprehensive genome-wide investigation of hearing loss (HL) in 748,668 adult participants of the UK Biobank, the Nurses’ Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program. We identified 54 risk loci and characterized HL polygenic architecture, exploring sex differences, polygenic risk across ancestries, tissue-specific transcriptomic regulation, cause-effect relationships with genetically-correlated traits, and gene interactions with HL environmental risk factors. Our transcriptomic regulation analysis highlighted the potential role of the central nervous system in HL pathogenesis. This was supported by the multivariate interaction analysis that showed how genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their HL associations. Additionally, the genetically-informed causal inference analysis showed that HL is linked to many physical and mental health outcomes. These results provide many novel insights into the complex biology and epidemiology of HL in adults.
Source: medRxiv
DOI: 10.1101/2022.01.26.22269898
Authors: Flavio De Angelis, Oana A. Zeleznik, Frank R. Wendt, Gita A. Pathak, Daniel S. Tylee, Antonella De Lillo, Dora Koller, Brenda Cabrera-Mendoza, Royce E Clifford, Adam X. Maihofer, Caroline M. Nievergelt, Gary C. Curhan, Sharon G. Curhan, Renato Polimanti
Institutions: Yale University, VA Connecticut Healthcare System, Brigham and Women's Hospital, Harvard University, University of Rome Tor Vergata, Universitat de Barcelona, University of California San Diego, VA San Diego Healthcare System, Center of Excellence for Stress and Mental Health
Language: English
Subfield: Sensory Systems
Open Access status: green
Funders: Office of Research and Development, One Mind, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, HORIZON EUROPE Marie Sklodowska-Curie Actions
Awards: G1416987869, G3090275372, Genome-wide Investigation of the Interplay Between Age-Related Hearing Loss and Smoking Behaviors, G4376790518, G4701187237, G526719173, G6200764915, Investigating the Systems Genetics of the Patterns of Polysubstance Abuse and Addiction, Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health Study
OpenAlex ID: W4210539250
Cites: 78
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Related to: 10