Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2302708120. doi: 10.1073/pnas.2302708120. Epub 2023 Jul 31.
To date, no study has explored the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of atrial fibrillation (AF). This study was designed to investigate the separate and joint effects of long-term exposure to air pollutants and genetic susceptibility on the risk of AF events. This study included 401,251 participants without AF at baseline from UK Biobank. We constructed a polygenic risk score and categorized it into three categories. Cox proportional hazards models were fitted to assess the separate and joint effects of long-term exposure to air pollutants and genetics on the risk of AF. Additionally, we further evaluated the effect modification of genetic susceptibility. The hazard ratios and corresponding 95% confidence intervals of incident AF for per interquartile range increase in particulate matter with an aerodynamic diameter smaller than 2.5 µm (PM) or 10 µm (PM), nitrogen dioxide (NO), and nitrogen oxide (NO) were 1.044 (1.025, 1.063), 1.063 (1.044, 1.083), 1.061 (1.042, 1.081), and 1.039 (1.023, 1.055), respectively. For the combined effects, participants exposed to high air pollutants levels and high genetic risk had approximately 149.2% (PM), 181.7% (PM), 170.2% (NO), and 157.2% (NO) higher risk of AF compared to those with low air pollutants levels and low genetic risk, respectively. Moreover, the significant additive interactions between PM and NO and genetic risk on AF risk were observed, with around 16.4% and 35.1% of AF risk could be attributable to the interactive effects. In conclusion, long-term exposure to air pollutants increases the risk of AF, particularly among individuals with high genetic susceptibility.
迄今为止，尚无研究探讨遗传易感性在多大程度上改变了空气污染物对心房颤动 (AF) 风险的影响。本研究旨在调查长期暴露于空气污染物和遗传易感性对 AF 事件风险的单独和联合影响。本研究纳入了英国生物库中 401,251 名基线无 AF 的参与者。我们构建了一个多基因风险评分，并将其分为三个类别。使用 Cox 比例风险模型评估长期暴露于空气污染物和遗传易感性对 AF 风险的单独和联合影响。此外，我们进一步评估了遗传易感性的效应修饰作用。对于每增加一个四分位间距的细颗粒物（PM）或 10 微米（PM）、二氧化氮（NO）和氮氧化物（NO），PM2.5 或 10µm 时的 AF 发生率的危险比（HR）和相应的 95%置信区间（CI）分别为 1.044（1.025，1.063）、1.063（1.044，1.083）、1.061（1.042，1.081）和 1.039（1.023，1.055）。对于联合效应，与低空气污染物水平和低遗传风险的参与者相比，暴露于高水平空气污染物和高遗传风险的参与者发生 AF 的风险分别约高 149.2%（PM）、181.7%（PM）、170.2%（NO）和 157.2%（NO）。此外，还观察到 PM 和 NO 与遗传风险对 AF 风险的显著相加交互作用，大约 16.4%和 35.1%的 AF 风险可归因于交互作用。总之，长期暴露于空气污染物会增加 AF 的风险，尤其是在遗传易感性高的个体中。
