Key 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.
Key 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.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117121. doi: 10.1016/j.ecoenv.2024.117121. Epub 2024 Oct 1.
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.
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 (NO), particulate matter (PM) with a diameter of ⩽2.5 μm (PM) and 2.5-10 μm (PM) 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.
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, NO, PM, and PM for Patient Health Questionnaire-9 (PHQ-9) score, and detected 44, 10, 10, and 114 candidate loci associated with NO, NO, PM, and PM for General Anxiety Disorder (GAD-7) score, respectively. And some significant genes overlapped among four air pollutants, like TSN (rs184699498, P = 3.47 × 10; rs139212326, P = 1.51 × 10) and HSP90AB7P(rs150987455, P = 1.63 × 10; rs150987455, P = 7.64 × 10), which were common genes affecting PHQ-9 score for both NO and PM.
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.
遗传因素和环境暴露，包括空气污染，都会增加抑郁和焦虑的风险。虽然空气污染与抑郁和焦虑之间的关系已在英国生物库研究中得到证实，但从遗传角度探索这种关系的研究有限。
基于英国生物库 104385 名参与者的个体基因型和表型数据，构建了抑郁和焦虑的多基因风险评分，以通过线性和逻辑回归模型探讨一氧化氮（NO）、二氧化氮（NO）、粒径 ⩽2.5μm（PM）和 2.5-10μm（PM）与抑郁和焦虑的联合效应。随后，使用 PLINK 2.0 进行全基因组基因-环境交互作用研究（GWEIS），以确定与空气污染相互作用的与抑郁和焦虑相关的基因。
在同时暴露于高空气污染和高遗传风险的参与者中，检测到明显的抑郁和焦虑发展风险。GWEIS 确定了 166、23、18 和 164 个与 NO、NO、PM 和 PM 与患者健康问卷-9（PHQ-9）评分相关的显著候选基因位点，并检测到 44、10、10 和 114 个与 NO、NO、PM 和 PM 与广泛性焦虑障碍（GAD-7）评分相关的候选基因位点。四个空气污染物之间存在一些显著的重叠基因，如 TSN（rs184699498，P = 3.47×10；rs139212326，P = 1.51×10）和 HSP90AB7P（rs150987455，P = 1.63×10；rs150987455，P = 7.64×10），这些基因是影响 NO 和 PM 两个因素的 PHQ-9 评分的共同基因。
本研究确定了空气污染与遗传易感性对抑郁和焦虑风险的联合影响，并为相互作用提供了几个新的候选基因，有助于了解抑郁和焦虑的遗传结构。
