Air pollution, genetic susceptibility, and the risk of atrial fibrillation: A large prospective cohort study

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 (PM2.5) or 10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxide (NOx) 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% (PM2.5), 181.7% (PM10), 170.2% (NO2), and 157.2% (NOx) higher risk of AF compared to those with low air pollutants levels and low genetic risk, respectively. Moreover, the significant additive interactions between PM10 and NO2 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.

Keywords: air pollutants; atrial fibrillation; genetic risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants* / adverse effects
  • Air Pollutants* / analysis
  • Air Pollution* / adverse effects
  • Air Pollution* / analysis
  • Atrial Fibrillation* / etiology
  • Atrial Fibrillation* / genetics
  • Environmental Exposure / adverse effects
  • Environmental Exposure / analysis
  • Genetic Predisposition to Disease
  • Humans
  • Nitric Oxide
  • Nitrogen Dioxide / adverse effects
  • Nitrogen Dioxide / analysis
  • Particulate Matter / adverse effects
  • Particulate Matter / analysis
  • Prospective Studies


  • Nitrogen Dioxide
  • Air Pollutants
  • Particulate Matter
  • Nitric Oxide