■以前的研究已经探讨了血浆蛋白在骨坏死中的作用。这项孟德尔随机化(MR)研究进一步评估了血浆蛋白对骨坏死是否存在因果关系,并提供了一些因果关系的证据。
■4,907个循环蛋白质水平的摘要水平数据是从由deCODE遗传学联盟进行的大规模蛋白质数量性状基因座研究中提取的,该研究包括35,559个个体。骨坏死的结果数据来自FinnGen研究,包括1,543例病例和391,037例对照。进行MR分析以评估蛋白质与骨坏死风险之间的关联。此外,全表型MR分析,和候选药物预测被用来识别潜在的因果循环蛋白和新的药物靶标。
■我们完全评估了1,676种血浆蛋白对骨坏死风险的影响,其中71种血浆蛋白与结局风险有暗示性关联(P<0.05).值得注意的是,血红素结合蛋白1(HEBP1)与骨坏死风险呈显著正相关(OR,1.40,95%CI,1.19~1.65,P=3.96×10-5,PFDR=0.044)。这种关联在其他MR分析方法中得到进一步证实,未检测到异质性和多效性(均P>0.05)。为全面探讨HEBP1对健康的影响,全表型MR分析发现,HEBP1与136种不包括骨坏死的表型相关(P<0.05)。然而,错误发现率调整后未观察到显著关联.
■这项全面的MR研究确定了71种与骨坏死相关的血浆蛋白,HEBP1,ITIH1,SMOC1和CREG1显示出作为骨坏死生物标志物的潜力。尽管如此,需要进一步的研究来验证该候选血浆蛋白.
UNASSIGNED: Previous studies have explored the role of plasma proteins on
osteonecrosis. This Mendelian randomization (MR) study further assessed plasma proteins on
osteonecrosis whether a causal relationship exists and provides some evidence of causality.
UNASSIGNED: Summary-level data of 4,907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals by the deCODE Genetics Consortium. The outcome data for osteonecrosis were sourced from the FinnGen study, comprising 1,543 cases and 391,037 controls. MR analysis was conducted to estimate the associations between protein and
osteonecrosis risk. Additionally, Phenome-wide MR analysis, and candidate drug prediction were employed to identify potential causal circulating proteins and novel drug targets.
UNASSIGNED: We totally assessed the effect of 1,676 plasma proteins on
osteonecrosis risk, of which 71 plasma proteins had a suggestive association with outcome risk (P < 0.05). Notably, Heme-binding protein 1 (HEBP1) was significant positively associated with osteonecrosis risk with convening evidence (OR, 1.40, 95% CI, 1.19 to 1.65, P = 3.96 × 10-5, P FDR = 0.044). This association was further confirmed in other MR analysis methods and did not detect heterogeneity and pleiotropy (all P > 0.05). To comprehensively explore the health effect of HEBP1, the phenome-wide MR analysis found it was associated with 136 phenotypes excluding osteonecrosis (P < 0.05). However, no significant association was observed after the false discovery rate adjustment.
UNASSIGNED: This comprehensive MR study identifies 71 plasma proteins associated with osteonecrosis, with HEBP1, ITIH1, SMOC1, and CREG1 showing potential as biomarkers of
osteonecrosis. Nonetheless, further studies are needed to validate this candidate plasma protein.