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However, there has not yet been a study investigating the joint association among genetics, lifestyle\/environmental factors, and adherence to healthy lifestyle for risk of ARHL. We aimed to assess the association between ARHL genetic variants, lifestyle\/environmental factors, and adherence to healthy lifestyle as pertains to risk of ARHL.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This case\u2013control study included 376,464 European individuals aged 40 to 69\u00a0years, enrolled between 2006 and 2010 in the UK Biobank (UKBB). As a replication set, we also included a total of 26,523 individuals considered of European ancestry and 9834 individuals considered of African-American ancestry through the Penn Medicine Biobank (PMBB). The polygenic risk score (PRS) for ARHL was derived from a sensorineural hearing loss genome-wide association study from the FinnGen Consortium and categorized as low, intermediate, high, and very high. We selected lifestyle\/environmental factors that have been previously studied in association with hearing loss. A composite healthy lifestyle score was determined using seven selected lifestyle behaviors and one environmental factor.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of the 376,464 participants, 87,066 (23.1%) cases belonged to the ARHL group, and 289,398 (76.9%) individuals comprised the control group in the UKBB. A very high PRS for ARHL had a 49% higher risk of ARHL than those with low PRS (adjusted OR, 1.49; 95% CI, 1.36\u20131.62; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001), which was replicated in the PMBB cohort. A very poor lifestyle was also associated with risk of ARHL (adjusted OR, 3.03; 95% CI, 2.75\u20133.35; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). These risk factors showed joint effects with the risk of ARHL. Conversely, adherence to healthy lifestyle in relation to hearing mostly attenuated the risk of ARHL even in individuals with very high PRS (adjusted OR, 0.21; 95% CI, 0.09\u20130.52; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings of this study demonstrated a significant joint association between genetic and lifestyle factors regarding ARHL. In addition, our analysis suggested that lifestyle adherence in individuals with high genetic risk could reduce the risk of ARHL.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12916-024-03364-5","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T12:02:49Z","timestamp":1711454569000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Association between genetic risk and adherence to healthy lifestyle for developing age-related hearing loss"],"prefix":"10.1186","volume":"22","author":[{"given":"Sang-Hyuk","family":"Jung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Chan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Shivakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Seung","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woong-Yang","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Hee","family":"Won","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Penn Medicine Biobank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4592-9564","authenticated-orcid":false,"given":"Dokyoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"issue":"9","key":"3364_CR1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a033217","volume":"8","author":"MR Bowl","year":"2019","unstructured":"Bowl MR, Dawson SJ. 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The present research using the UKBB Resource was approved under Application Number 33002. The collection, storage, and analysis of biospecimens, genetic data, and data derived from electronic health records as part of the Penn Medicine Biobank (PMBB) is approved under University of Pennsylvania IRB protocol #813913. Participants from the UKBB and the PMBB provided written informed consent allowing use of their samples and data for medical research purposes. This study followed the reporting requirements of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"141"}}