循环炎症蛋白对骨质疏松症和骨折的影响：来自遗传关联和孟德尔随机化研究的证据。
Effects of circulating inflammatory proteins on osteoporosis and fractures: evidence from genetic correlation and Mendelian randomization study.
机构信息
Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Arthritis Clinical and Research Center, Peking University People's Hospital, Beijing, China.
出版信息
Front Endocrinol (Lausanne). 2024 May 1;15:1386556. doi: 10.3389/fendo.2024.1386556. eCollection 2024.
OBJECTIVE
There is a controversy in studies of circulating inflammatory proteins (CIPs) in association with osteoporosis (OP) and fractures, and it is unclear if these two conditions are causally related. This study used MR analyses to investigate the causal associations between 91 CIPs and OP and 9 types of fractures.
METHODS
Genetic variants data for CIPs, OP, and fractures were obtained from the publicly available genome-wide association studies (GWAS) database. We used inverse variance weighted (IVW) as the primary analysis, pleiotropy, and heterogeneity tests to analyze the validity and robustness of causality and reverse MR analysis to test for reverse causality.
RESULTS
The IVW results with Bonferroni correction indicated that CXCL11 (OR = 1.2049; 95% CI: 1.0308-1.4083; = 0.0192) can increase the risk of OP; IL-4 (OR = 1.2877; 95% CI: 1.1003-1.5070; = 0.0016), IL-7 (OR = 1.2572; 95% CI: 1.0401-1.5196; = 0.0180), IL-15RA (OR = 1.1346; 95% CI: 1.0163-1.2668; = 0.0246), IL-17C (OR = 1.1353; 95% CI: 1.0272-1.2547; = 0.0129), CXCL10 (OR = 1.2479; 95% CI: 1.0832-1.4377; = 0.0022), eotaxin/CCL11 (OR = 1.1552; 95% CI: 1.0525-1.2678; = 0.0024), and FGF23 (OR = 1.9437; 95% CI: 1.1875-3.1816; = 0.0082) can increase the risk of fractures; whereas IL-10RB (OR = 0.9006; 95% CI: 0.8335-0.9730; = 0.0080), CCL4 (OR = 0.9101; 95% CI: 0.8385-0.9878; = 0.0242), MCP-3/CCL7 (OR = 0.8579; 95% CI: 0.7506-0.9806; = 0.0246), IFN-γ [shoulder and upper arm (OR = 0.7832; 95% CI: 0.6605-0.9287; = 0.0049); rib(s), sternum and thoracic spine (OR = 0.7228; 95% CI: 0.5681-0.9197; = 0.0083)], β-NGF (OR = 0.8384; 95% CI: 0.7473-0.9407; = 0.0027), and SIRT2 (OR = 0.5167; 95% CI: 0.3296-0.8100; = 0.0040) can decrease fractures risk.
CONCLUSION
Mendelian randomization (MR) analyses indicated the causal associations between multiple genetically predicted CIPs and the risk of OP and fractures.
目的
循环炎症蛋白 (CIP) 与骨质疏松症 (OP) 和骨折的关联研究存在争议，目前尚不清楚这两种情况是否存在因果关系。本研究使用 MR 分析来研究 91 种 CIP 与 OP 和 9 种骨折类型之间的因果关系。
方法
从公开的全基因组关联研究 (GWAS) 数据库中获取 CIP、OP 和骨折的遗传变异数据。我们使用逆方差加权 (IVW) 作为主要分析方法，进行 pleiotropy 和异质性检验来分析因果关系的有效性和稳健性，以及进行反向 MR 分析来检验反向因果关系。
结果
经 Bonferroni 校正的 IVW 结果表明，CXCL11（OR=1.2049；95%CI：1.0308-1.4083； = 0.0192）可增加 OP 的发病风险；IL-4（OR=1.2877；95%CI：1.1003-1.5070； = 0.0016）、IL-7（OR=1.2572；95%CI：1.0401-1.5196； = 0.0180）、IL-15RA（OR=1.1346；95%CI：1.0163-1.2668； = 0.0246）、IL-17C（OR=1.1353；95%CI：1.0272-1.2547； = 0.0129）、CXCL10（OR=1.2479；95%CI：1.0832-1.4377； = 0.0022）、eotaxin/CCL11（OR=1.1552；95%CI：1.0525-1.2678； = 0.0024）和 FGF23（OR=1.9437；95%CI：1.1875-3.1816； = 0.0082）可增加骨折的发病风险；而 IL-10RB（OR=0.9006；95%CI：0.8335-0.9730； = 0.0080）、CCL4（OR=0.9101；95%CI：0.8385-0.9878； = 0.0242）、MCP-3/CCL7（OR=0.8579；95%CI：0.7506-0.9806； = 0.0246）、IFN-γ[肩部和上臂（OR=0.7832；95%CI：0.6605-0.9287； = 0.0049）；肋骨、胸骨和胸椎（OR=0.7228；95%CI：0.5681-0.9197； = 0.0083）]、β-NGF（OR=0.8384；95%CI：0.7473-0.9407； = 0.0027）和 SIRT2（OR=0.5167；95%CI：0.3296-0.8100； = 0.0040）可降低骨折风险。
结论
Mendelian randomization（MR）分析表明，多种遗传预测的 CIP 与 OP 和骨折的风险之间存在因果关系。
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