Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis

Qinghua Fan, Shifeng Wen, Yi Zhang,Xiuming Feng, Wanting Zheng, Xiaolin Liang, Yutong Lin,Shimei Zhao, Kaisheng Xie, Hancheng Jiang, Haifeng Tang, Xiangtai Zeng,You Guo, Wang Fei,Xiaobo Yang

iScience(2024)

引用 0|浏览11
暂无评分
摘要
The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC Meta-GWAS (nCase=3418, nControl=292703) to conduct Proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expression were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections (PBH=3.28e-5, 0.05/1525). These proteins were involved in amino acids and organic acid synthesis pathways. Colocalization analysis further identified six proteins (PP.H4 > 0.5) associated with TCs (VCAM1, LGMN, NPTX1, PLEKHA7, TNFAIP3, and BMP1). Tissue validation confirmed BMP1, LGMN, and PLEKHA7's differential expression between normal and TC tissues. We found limited evidence for linking circulating proteins and the risk of TCs. Our study highlighted the contribution of proteins, particularly those involved in amino acid metabolism, to TCs.
更多
查看译文
关键词
computational bioinformatics,cancer
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要