Genetic susceptibility and lifestyle modify the association of long-term air pollution exposure on major depressive disorder: a prospective study in UK Biobank

Abstract

Background: Evidence linking air pollution to major depressive disorder (MDD) remains sparse and results are heterogeneous. In addition, the evidence about the interaction and joint associations of genetic risk and lifestyle with air pollution on incident MDD risk remains unclear. We aimed to examine the association of various air pollutants with the risk of incident MDD and assessed whether genetic susceptibility and lifestyle influence the associations.

Methods: This population-based prospective cohort study analyzed data collected between March 2006 and October 2010 from 354,897 participants aged 37 to 73 years from the UK Biobank. Annual average concentrations of PM_2.5, PM₁₀, NO₂, and NO_x were estimated using a Land Use Regression model. A lifestyle score was determined based on a combination of smoking, alcohol drinking, physical activity, television viewing time, sleep duration, and diet. A polygenic risk score (PRS) was defined using 17 MDD-associated genetic loci.

Results: During a median follow-up of 9.7 years (3,427,084 person-years), 14,710 incident MDD events were ascertained. PM_2.5 (HR: 1.16, 95% CI: 1.07-1.26; per 5 μg/m³) and NO_x (HR: 1.02, 95% CI: 1.01-1.05; per 20 μg/m³) were associated with increased risk of MDD. There was a significant interaction between the genetic susceptibility and air pollution for MDD (P-interaction < 0.05). Compared with participants with low genetic risk and low air pollution, those with high genetic risk and high PM_2.5 exposure had the highest risk of incident MDD (PM_2.5: HR: 1.34, 95% CI: 1.23-1.46). We also observed an interaction between PM_2.5 exposure and unhealthy lifestyle (P-interaction < 0.05). Participants with the least healthy lifestyle and high air pollution exposures had the highest MDD risk when compared to those with the most healthy lifestyle and low air pollution (PM_2.5: HR: 2.22, 95% CI: 1.92-2.58; PM₁₀: HR: 2.09, 95% CI: 1.78-2.45; NO₂: HR: 2.11, 95% CI: 1.82-2.46; NO_x: HR: 2.28, 95% CI: 1.97-2.64).

Conclusions: Long-term exposure to air pollution is associated with MDD risk. Identifying individuals with high genetic risk and developing healthy lifestyle for reducing the harm of air pollution to public mental health.

Keywords: Air pollution; Genetic susceptibility; Healthy lifestyle; Interaction; Major depressive disorder.

Fig. 1

Dose–response relationship of long-term exposure to air pollution and incident major depressive disorder (MDD). Multiple-adjusted hazard ratio (HR) for continuous air pollution is modeled using restricted cubic splines. Models are adjusted for age, gender, ethnicity, education level, employment status, household income, and Townsend deprivation index. The reference group is considered the minimum exposure level of air pollution in the entire population. Gray bars represent the distribution of the exposure levels in the entire population. The blue solid line indicates HR and the shaded area indicates a 95% confidence interval

Fig. 2

Joint associations of genetic risk score with incident major depressive disorder (MDD). Hazard ratios were adjusted for age, gender, ethnicity, education level, employment status, household income, and Townsend deprivation index. The interaction between genetic risk with air pollutants was tested by stratifying genetic risk

Fig. 3

Joint associations of healthy lifestyle score with incident major depressive disorder (MDD). Hazard ratios were adjusted for age, gender, ethnicity, education level, employment status, household income, and Townsend deprivation index. The interaction between lifestyle with air pollutants was tested by stratifying lifestyle categories