Enhanced polygenic risk score incorporating gene-environment interaction suggests the association of major depressive
Chuyu Pan1, Bolun Cheng1, Xiaoyue Qin1
1Key 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.
Background:
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.
Methods:
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.
Results:
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).
Conclusions:
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.
More Related Videos
05:53Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
10:21Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
Related Concept Videos
01:28Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
01:20Gene-Environment Interactions
01:18Polygenic Traits
02:27Background and Environment Affect Phenotype
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
01:27Psychoneuroimmunology: Cardiovascular Disease
A key area of focus in PNI is the relationship between stress and coronary...