Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits
Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits
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DOI：
10.1136/ard-2023-224459
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发表时间：
2023-08
影响因子：
27.4
通讯作者：
Yan Zhang;Jingyu Xie;Simin Wen;P. Cao;Wende Xiao;Jianwei Zhu;Shengfa Li;Zhiqiang Wang;Hana Cen;Zhaohua Zhu;C. Ding;G. Ruan
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文献类型：
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作者：
Yan Zhang;Jingyu Xie;Simin Wen;P. Cao;Wende Xiao;Jianwei Zhu;Shengfa Li;Zhiqiang Wang;Hana Cen;Zhaohua Zhu;C. Ding;G. Ruan
目的本研究旨在通过基于孟德尔随机化（MR）的分析框架来鉴定与骨关节炎（OA）相关性状因果相关的循环蛋白。方法采用大规模双样本MR方法，研究了上千种血浆蛋白对12个OA相关性状的影响。进行了其他分析，包括贝叶斯共定位，Steiger过滤分析，蛋白质改变变体的评估和表达数量性状基因座与蛋白质数量性状基因座的映射，以研究MR结果的可靠性;进行了蛋白质-蛋白质相互作用，途径富集分析和药物靶点评价，以加深对OA的理解并确定潜在的治疗靶点。结果发现了几十种循环蛋白对OA相关性状具有致腐作用，其中大多数蛋白是药物靶点或可药用蛋白。结论通过MR分析，我们已经确定了许多与OA相关性状相关的血浆蛋白，阐明了蛋白质介导的机制，并为OA提供了有希望的治疗靶点。
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.