Association between genetically plasma proteins and osteonecrosis: a proteome-wide Mendelian randomization analysis
Meng, C; Ren, JX; Gu, HL; Shi, HX; Luo, H; Wang, ZH; Li, C; Xu, YQ
2024
发表期刊FRONT GENET
卷号15
摘要Background: 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. Methods: 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. Results: 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 x 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. Conclusion: 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.
收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/14597
专题科研部门_天然药物功能蛋白质学科组(赖仞)
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GB/T 7714
Meng, C,Ren, JX,Gu, HL,et al. Association between genetically plasma proteins and osteonecrosis: a proteome-wide Mendelian randomization analysis[J]. FRONT GENET,2024,15.
APA Meng, C.,Ren, JX.,Gu, HL.,Shi, HX.,Luo, H.,...&Xu, YQ.(2024).Association between genetically plasma proteins and osteonecrosis: a proteome-wide Mendelian randomization analysis.FRONT GENET,15.
MLA Meng, C,et al."Association between genetically plasma proteins and osteonecrosis: a proteome-wide Mendelian randomization analysis".FRONT GENET 15(2024).
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