| Title: | Proteome-wide Mendelian randomization identifies causal plasma proteins in lung cancer |
| Journal: | iScience |
| Published: | 20 Jan 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38333712/ |
| DOI: | https://doi.org/10.1016/j.isci.2024.108985 |
Publication 8912
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Abstract
Plasma proteins are promising biomarkers and potential drug targets in lung cancer. To evaluate the causal association between plasma proteins and lung cancer, we performed proteome-wide Mendelian randomization meta-analysis (PW-MR-meta) based on lung cancer genome-wide association studies (GWASs), protein quantitative trait loci (pQTLs) of 4,719 plasma proteins in deCODE and 4,775 in Fenland. Further, causal-protein risk score (CPRS) was developed based on causal proteins and validated in the UK Biobank. 270 plasma proteins were identified using PW-MR meta-analysis, including 39 robust causal proteins (both FDR-q < 0.05) and 78 moderate causal proteins (FDR-q < 0.05 in one and p < 0.05 in another). The CPRS had satisfactory performance in risk stratification for lung cancer (top 10% CPRS:Hazard ratio (HR) (95%CI):4.33(2.65-7.06)). The CPRS [AUC (95%CI): 65.93 (62.91-68.78)] outperformed the traditional polygenic risk score (PRS) [AUC (95%CI): 55.71(52.67-58.59)]. Our findings offer further insight into the genetic architecture of plasma proteins for lung cancer susceptibility.</p>
13 Authors
- Hongru Li
- Sha Du
- Jinglan Dai
- Yunke Jiang
- Zaiming Li
- Qihan Fan
- Yixin Zhang
- Dongfang You
- Ruyang Zhang
- Yang Zhao
- David C. Christiani
- Sipeng Shen
- Feng Chen
1 Application
| Application ID | Title |
|---|---|
| 92675 | Study on the association between wide environmental exposure factors and common chronic diseases |
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