Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China, Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, P. R. China.
Brief Bioinform. 2024 Jan 22;25(2). doi: 10.1093/bib/bbae070.
Depression has been linked to an increased risk of cardiovascular and respiratory diseases; however, its impact on cardiac and lung function remains unclear, especially when accounting for potential gene-environment interactions.
We developed a novel polygenic and gene-environment interaction risk score (PGIRS) integrating the major genetic effect and gene-environment interaction effect of depression-associated loci. The single nucleotide polymorphisms (SNPs) demonstrating major genetic effect or environmental interaction effect were obtained from genome-wide SNP association and SNP-environment interaction analyses of depression. We then calculated the depression PGIRS for non-depressed individuals, using smoking and alcohol consumption as environmental factors. Using linear regression analysis, we assessed the associations of PGIRS and conventional polygenic risk score (PRS) with lung function (N = 42 886) and cardiac function (N = 1791) in the subjects with or without exposing to smoking and alcohol drinking.
We detected significant associations of depression PGIRS with cardiac and lung function, contrary to conventional depression PRS. Among smokers, forced vital capacity exhibited a negative association with PGIRS (β = -0.037, FDR = 1.00 × 10-8), contrasting with no significant association with PRS (β = -0.002, FDR = 0.943). In drinkers, we observed a positive association between cardiac index with PGIRS (β = 0.088, FDR = 0.010), whereas no such association was found with PRS (β = 0.040, FDR = 0.265). Notably, in individuals who both smoked and drank, forced expiratory volume in 1-second demonstrated a negative association with PGIRS (β = -0.042, FDR = 6.30 × 10-9), but not with PRS (β = -0.003, FDR = 0.857).
Our findings underscore the profound impact of depression on cardiac and lung function, highlighting the enhanced efficacy of considering gene-environment interactions in PRS-based studies.
抑郁症与心血管和呼吸系统疾病的风险增加有关；然而，其对心脏和肺部功能的影响尚不清楚，特别是在考虑到潜在的基因-环境相互作用时。
我们开发了一种新的多基因和基因-环境相互作用风险评分（PGIRS），该评分综合了与抑郁症相关的基因座的主要遗传效应和基因-环境相互作用效应。具有主要遗传效应或环境相互作用效应的单核苷酸多态性（SNP）是从抑郁症的全基因组 SNP 关联和 SNP-环境相互作用分析中获得的。然后，我们使用吸烟和饮酒作为环境因素，为非抑郁个体计算抑郁 PGIRS。我们使用线性回归分析评估了 PGIRS 和传统多基因风险评分（PRS）与暴露于吸烟和饮酒的个体的心肺功能（N=42886）和心脏功能（N=1791）的相关性。
我们检测到抑郁 PGIRS 与心肺功能显著相关，而与传统的抑郁 PRS 相反。在吸烟者中，用力肺活量与 PGIRS 呈负相关（β=-0.037，FDR=1.00×10-8），而与 PRS 无显著相关性（β=-0.002，FDR=0.943）。在饮酒者中，我们观察到心脏指数与 PGIRS 呈正相关（β=0.088，FDR=0.010），而与 PRS 无相关性（β=0.040，FDR=0.265）。值得注意的是，在同时吸烟和饮酒的个体中，一秒用力呼气量与 PGIRS 呈负相关（β=-0.042，FDR=6.30×10-9），而与 PRS 无相关性（β=-0.003，FDR=0.857）。
我们的研究结果强调了抑郁症对心肺功能的深远影响，突出了在 PRS 研究中考虑基因-环境相互作用的增强功效。
