BACKGROUND Unraveling gene-environment interaction can provide a novel insight into early disease prevention. Nevertheless, current understanding of the interplay between genetic predisposition and air pollution in relation to myocardial infarction (MI) risk remains limited. Furthermore, the potential long-term influence of air pollutants on MI incidence risk warrants more conclusive evidence in a community population. OBJECTIVE We investigated interactions between genetic predisposition and exposure to air pollutants on MI incidence. METHODS This study incorporated a sample of 456,354 UK Biobank participants and annual mean air pollution (PM2.5, PM10, NO2, and NOx) from the UK Department for Environment, Food and Rural Affairs (2006-2021). The Cox proportional hazards model was employed to explore MI incidence after chronic air pollutants exposure. By quantifying genetic risk through the calculation of polygenic risk score (PRS), this study further examined the interactions between genetic risk and exposure to air pollutants in the development of MI on both additive and multiplicative scales. RESULTS Among 456,354 participants, 9,114 incident MI events were observed during a median follow-up of 12.08 y. Chronic exposure to air pollutants was linked with an increased risk of MI occurrence. Specifically, the hazard ratios (per interquartile range) were 1.12 (95% CI: 1.10, 1.13) for PM2.5, 1.20 (95% CI: 1.19, 1.22) for PM10, 1.13 (95% CI: 1.12, 1.15) for NO2, and 1.12 (95% CI: 1.11, 1.13) for NOx. In terms of the joint effects, participants with high PRS and high level of air pollution exposure exhibited the greatest risk of MI among all study participants (∼255% to 324%). Remarkably, both multiplicative and additive interactions were detected in the ambient air pollutants exposure and genetic risk on the incidence of MI. DISCUSSION There were interactions between exposure to ambient air pollutants and genetic susceptibility on the risk of MI onset. Moreover, the joint effects of these two exposures were greater than the effect of each factor alone. https://doi.org/10.1289/EHP14291.

中文翻译：

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暴露于空气污染物和心肌梗死发生率：一项探索基因-环境相互作用的英国生物样本库研究。


背景 揭示基因-环境相互作用可以为早期疾病预防提供新的见解。然而，目前对遗传易感性和空气污染与心肌梗死 （MI） 风险之间的相互作用的理解仍然有限。此外，空气污染物对 MI 发病率风险的潜在长期影响需要在社区人群中提供更确凿的证据。目的 我们研究了遗传易感性与空气污染物暴露对 MI 发病率的相互作用。方法 本研究纳入了 456,354 名英国生物样本库参与者和来自英国环境、食品和农村事务部（2006-2021 年）的年平均空气污染（PM2.5、PM10、NO2 和 NOx）。采用 Cox 比例风险模型来探索慢性空气污染物暴露后的 MI 发生率。通过计算多基因风险评分 （PRS） 量化遗传风险，本研究在加法和乘法量表上进一步考察了遗传风险与暴露于 MI 发展过程中空气污染物之间的相互作用。结果 在 456,354 名参与者中，在中位随访 12.08 年期间观察到 9,114 例 MI 事件。长期暴露于空气污染物与 MI 发生风险增加有关。具体而言，PM2.5 的风险比（每四分位距）为 1.12 （95% CI： 1.10， 1.13），PM10 为 1.20 （95% CI： 1.19， 1.22），NO2 为 1.13 （95% CI： 1.12， 1.15） 和 NOx 为 1.12 （95% CI： 1.11， 1.13）。就联合效应而言，在所有研究参与者中，具有高 PRS 和高水平空气污染暴露的参与者表现出最大的 MI 风险（∼255% 至 324%）。 值得注意的是，在环境空气污染物暴露和 MI 发病率的遗传风险中检测到乘性和加性相互作用。讨论 暴露于环境空气污染物与遗传易感性对 MI 发病风险之间存在相互作用。此外，这两种暴露的联合效应大于单独每个因素的影响。https://doi.org/10.1289/EHP14291。