Previous studies have shown that lifestyle/environmental factors could accelerate the development of age-related hearing loss (ARHL). 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. This case–control study included 376,464 European individuals aged 40 to 69 years, 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. 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, 1.36–1.62; P < .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, 2.75–3.35; P < .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, 0.09–0.52; P < .001). 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.

中文翻译：

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遗传风险与坚持健康生活方式与年龄相关性听力损失之间的关系

先前的研究表明，生活方式/环境因素可能会加速年龄相关性听力损失（ARHL）的发展。然而，目前还没有一项研究调查遗传、生活方式/环境因素以及坚持健康生活方式与 ARHL 风险之间的联合关系。我们的目的是评估 ARHL 遗传变异、生活方式/环境因素以及坚持健康生活方式与 ARHL 风险之间的关联。这项病例对照研究纳入了 2006 年至 2010 年间在英国生物银行 (UKBB) 登记的 376,464 名 40 至 69 岁欧洲个体。作为复制集，我们还通过 Penn Medicine Biobank (PMBB) 纳入了总共 26,523 名欧洲血统个体和 9834 名非裔美国人血统个体。 ARHL 的多基因风险评分 (PRS) 来自 FinnGen 联盟的感音神经性听力损失全基因组关联研究，分为低、中、高和极高。我们选择了之前研究过的与听力损失相关的生活方式/环境因素。使用七种选定的生活方式行为和一种环境因素来确定综合健康生活方式得分。在 376,464 名参与者中，87,066 例（23.1%）属于 ARHL 组，289,398 例（76.9%）属于 UKBB 对照组。 ARHL 的 PRS 非常高的患者发生 ARHL 的风险比 PRS 低的患者高 49%（调整后 OR，1.49；95% CI，1.36–1.62；P < .001），这在 PMBB 队列中得到了重复。非常不良的生活方式也与 ARHL 风险相关（调整后 OR，3.03；95% CI，2.75–3.35；P < .001）。这些危险因素与 ARHL 风险存在共同影响。相反，即使对于 PRS 非常高的个体，坚持与听力相关的健康生活方式也能很大程度上降低 ARHL 的风险（调整后 OR，0.21；95% CI，0.09–0.52；P < .001）。我们的研究结果表明，与 ARHL 相关的遗传因素和生活方式因素之间存在显着的联合关联。此外，我们的分析表明，遗传风险高的个体坚持生活方式可以降低 ARHL 的风险。