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A genome-wide gene-environmental interaction study identified novel loci for the relationship between ambient air

Peilin Meng¹, Chuyu Pan¹, Xiaoyue Qin¹

¹Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

Ecotoxicology and Environmental Safety

|October 2, 2024

Abstract

Background:

Genetic factors and environmental exposures, including air pollution, contribute to the risk of depression and anxiety. While the association between air pollution and depression and anxiety has been established in the UK Biobank, there has been limited research exploring this relationship from a genetic perspective.

Methods:

Based on individual genotypic and phenotypic data from a cohort of 104,385 participants in the UK Biobank, a polygenic risk score for depression and anxiety was constructed to explore the joint effects of nitric oxide (NO), nitrogen dioxide (NO₂), particulate matter (PM) with a diameter of ⩽2.5 μm (PM_2.5) and 2.5-10 μm (PM_coarse) with depression and anxiety by linear and logistic regression models. Subsequently, a genome-wide gene-environmental interaction study (GWEIS) was performed using PLINK 2.0 to identify the genes interacting with air pollution for depression and anxiety.

Results:

A substantial risk of depression and anxiety development was detected in participants exposed to the high air pollution concomitantly with high genetic risk. GWEIS identified 166, 23, 18, and 164 significant candidate loci interacting with NO, NO₂, PM_2.5, and PM_coarse for Patient Health Questionnaire-9 (PHQ-9) score, and detected 44, 10, 10, and 114 candidate loci associated with NO, NO₂, PM_2.5, and PM_coarse for General Anxiety Disorder (GAD-7) score, respectively. And some significant genes overlapped among four air pollutants, like TSN (rs184699498, P_NO2 = 3.47 × 10^-9; rs139212326, P_PM2.5 = 1.51 × 10^-8) and HSP90AB7P(rs150987455, P_NO2 = 1.63 × 10^-11; rs150987455, P_PM2.5 = 7.64 × 10^-11), which were common genes affecting PHQ-9 score for both NO₂ and PM_2.5.

Conclusion:

Our study identified the joint effects of air pollution with genetic susceptibility on the risk of depression and anxiety, and provided several novel candidate genes for the interaction, contributing to an understanding of the genetic architecture of depression and anxiety.

Keywords:

Air pollution Anxiety Depression Genetic susceptibility Genome-wide gene-environmental interaction study

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