评估循环蛋白质组对骨关节炎相关特征风险的因果效应。

Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits.

机构信息

Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Ann Rheum Dis. 2023 Dec;82(12):1606-1617. doi: 10.1136/ard-2023-224459. Epub 2023 Aug 18.

DOI:10.1136/ard-2023-224459

PMID:37595989

Abstract

OBJECTIVES

This study aims to identify circulating proteins that are causally associated with osteoarthritis (OA)-related traits through Mendelian randomisation (MR)-based analytical framework.

METHODS

Large-scale two-sample MR was employed to estimate the effects of thousands of plasma proteins on 12 OA-related traits. Additional analyses including Bayesian colocalisation, Steiger filtering analysis, assessment of protein-altering variants and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings; protein-protein interaction, pathway enrichment analysis and evaluation of drug targets were conducted to deepen the understanding and identify potential therapeutic targets of OA.

RESULTS

Dozens of circulating proteins were identified to have putatively causal effects on OA-related traits, and a majority of these proteins were either drug targets or considered druggable.

CONCLUSIONS

Through MR analysis, we have identified numerous plasma proteins associated with OA-related traits, shedding light on protein-mediated mechanisms and offering promising therapeutic targets for OA.

摘要

目的

本研究旨在通过基于孟德尔随机化（MR）的分析框架，确定与骨关节炎（OA）相关特征有因果关系的循环蛋白。

方法

采用大规模两样本 MR 方法，估计数千种血浆蛋白对 12 种 OA 相关特征的影响。还进行了包括贝叶斯共定位、Steiger 过滤分析、蛋白改变变体评估以及将表达数量性状基因座映射到蛋白数量性状基因座的额外分析，以探讨 MR 结果的可靠性；进行了蛋白-蛋白相互作用、途径富集分析和药物靶点评估，以加深对 OA 的理解并确定潜在的治疗靶点。