| Title: | Enhanced polygenic risk score incorporating gene-environment interaction suggests the association of major depressive disorder with cardiac and lung function |
| Journal: | Briefings in Bioinformatics |
| Published: | 22 Jan 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38436562/ |
| DOI: | https://doi.org/10.1093/bib/bbae070 |
| URL: | https://academic.oup.com/bib/article-pdf/25/2/bbae070/56822148/bbae070.pdf |
Publication 8908
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Abstract
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.</p>
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.</p>
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).</p>
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.</p>
16 Authors
- Chuyu Pan
- Bolun Cheng
- Xiaoyue Qin
- Shiqiang Cheng
- Li Liu
- Xuena Yang
- Peilin Meng
- Na Zhang
- Dan He
- Qingqing Cai
- Wenming Wei
- Jingni Hui
- Yan Wen
- Yumeng Jia
- Huan Liu
- Feng Zhang
1 Application
| Application ID | Title |
|---|---|
| 46478 | Multi-omics integrative studies of common psychiatric disorders and skeletal disorders |
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