| Title: | Proteome-wide mendelian randomization identifies causal plasma proteins in venous thromboembolism development |
| Journal: | Journal of Human Genetics |
| Published: | 3 Aug 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37537391/ |
| DOI: | https://doi.org/10.1038/s10038-023-01186-6 |
| URL: | https://www.nature.com/articles/s10038-023-01186-6.pdf |
Publication 7701
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Abstract
Genome-wide association studies (GWAS) have identified numerous risk loci for venous thromboembolism (VTE), but it is challenging to decipher the underlying mechanisms. We employed an integrative analytical pipeline to transform genetic associations to identify novel plasma proteins for VTE. Proteome-wide association studies (PWAS) were determined by functional summary-based imputation leveraging data from a genome-wide association analysis (14,429 VTE patients, 267,037 controls), blood proteomes (1348 cases), followed by Mendelian randomization, Bayesian colocalization, protein-protein interaction, and pathway enrichment analysis. Twenty genetically regulated circulating protein abundances (F2, F11, ABO, PLCG2, LRP4, PLEK, KLKB1, PROC, KNG1, THBS2, SERPINA1, RARRES2, CEL, GP6, SERPINE2, SERPINA10, OBP2B, EFEMP1, F5, and MSR1) were associated with VTE. Of these 13 proteins demonstrated Mendelian randomized correlations. Six proteins (F2, F11, PLEK, SERPINA1, RARRES2, and SERPINE2) had strong support in colocalization analysis. Utilizing multidimensional data, this study suggests PLEK, SERPINA1, and SERPINE2 as compelling proteins that may provide key hints for future research and possible diagnostic and therapeutic targets for VTE.16 Authors
- Haobo Li
- Zhu Zhang
- Yuting Qiu
- Haoyi Weng
- Shuai Yuan
- Yunxia Zhang
- Yu Zhang
- Linfeng Xi
- Feiya Xu
- Xiaofan Ji
- Risheng Hao
- Peiran Yang
- Gang Chen
- Xianbo Zuo
- Zhenguo Zhai
- Chen Wang
1 Application
| Application ID | Title |
|---|---|
| 56719 | Comparative genetic and analysis of pulmonary diseases across different races |
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