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Effects of circulating inflammatory proteins on osteoporosis and fractures: evidence from genetic correlation and Mendelian randomization study.
- Source :
-
Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 May 01; Vol. 15, pp. 1386556. Date of Electronic Publication: 2024 May 01 (Print Publication: 2024). - Publication Year :
- 2024
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Abstract
- 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.<br />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.<br />Results: The IVW results with Bonferroni correction indicated that CXCL11 (OR = 1.2049; 95% CI: 1.0308-1.4083; P = 0.0192) can increase the risk of OP; IL-4 (OR = 1.2877; 95% CI: 1.1003-1.5070; P = 0.0016), IL-7 (OR = 1.2572; 95% CI: 1.0401-1.5196; P = 0.0180), IL-15RA (OR = 1.1346; 95% CI: 1.0163-1.2668; P = 0.0246), IL-17C (OR = 1.1353; 95% CI: 1.0272-1.2547; P = 0.0129), CXCL10 (OR = 1.2479; 95% CI: 1.0832-1.4377; P = 0.0022), eotaxin/CCL11 (OR = 1.1552; 95% CI: 1.0525-1.2678; P = 0.0024), and FGF23 (OR = 1.9437; 95% CI: 1.1875-3.1816; P = 0.0082) can increase the risk of fractures; whereas IL-10RB (OR = 0.9006; 95% CI: 0.8335-0.9730; P = 0.0080), CCL4 (OR = 0.9101; 95% CI: 0.8385-0.9878; P = 0.0242), MCP-3/CCL7 (OR = 0.8579; 95% CI: 0.7506-0.9806; P = 0.0246), IFN-γ [shoulder and upper arm (OR = 0.7832; 95% CI: 0.6605-0.9287; P = 0.0049); rib(s), sternum and thoracic spine (OR = 0.7228; 95% CI: 0.5681-0.9197; P = 0.0083)], β-NGF (OR = 0.8384; 95% CI: 0.7473-0.9407; P = 0.0027), and SIRT2 (OR = 0.5167; 95% CI: 0.3296-0.8100; P = 0.0040) can decrease fractures risk.<br />Conclusion: Mendelian randomization (MR) analyses indicated the causal associations between multiple genetically predicted CIPs and the risk of OP and fractures.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2024 Zheng, Wang, Lin, Li, Chen, Chen, Zheng and Xu.)
- Subjects :
- Humans
Fractures, Bone genetics
Fractures, Bone blood
Fractures, Bone epidemiology
Polymorphism, Single Nucleotide
Fibroblast Growth Factor-23
Genetic Predisposition to Disease
Female
Osteoporotic Fractures genetics
Osteoporotic Fractures blood
Osteoporotic Fractures epidemiology
Mendelian Randomization Analysis
Osteoporosis genetics
Osteoporosis blood
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 1664-2392
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- Frontiers in endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 38757000
- Full Text :
- https://doi.org/10.3389/fendo.2024.1386556