Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma

Abstract Objective To investigate the causal relationship between 91 circulating inflammatory proteins and osteosarcoma using the two-sample Mendelian randomization method. Method Corresponding exposure and outcome data were extracted from genome-wide association study (GWAS) databases. A two-sample...

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Main Authors: Hong Tang, Na Tang, Yueling Liao, Tao Tan, Hui Xie, Jiong Wang, Xie Hui
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03283-8
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author Hong Tang
Na Tang
Yueling Liao
Tao Tan
Hui Xie
Jiong Wang
Xie Hui
author_facet Hong Tang
Na Tang
Yueling Liao
Tao Tan
Hui Xie
Jiong Wang
Xie Hui
author_sort Hong Tang
collection DOAJ
description Abstract Objective To investigate the causal relationship between 91 circulating inflammatory proteins and osteosarcoma using the two-sample Mendelian randomization method. Method Corresponding exposure and outcome data were extracted from genome-wide association study (GWAS) databases. A two-sample Mendelian randomization analysis was conducted on the data, with the inverse-variance weighted (IVW) method serving as the primary analytical approach. This was complemented by MR-Egger, weighted median, simple mode, and weighted mode methods to validate the results. Sensitivity analyses were also performed to verify the reliability of the data. Results The IVW analysis revealed a positive causal relationship between GCST90274776 (OR = 3.02, 95% CI: 0.033–0.117, P = 0.028), GCST90274822 (OR = 1.603, 95% CI: 1.014–2.535, P = 0.043), and GCST90274847 (OR = 2.580, 95% CI: 1.155–5.762, P = 0.021) and osteosarcoma. In contrast, GCST90274844 (OR = 0.313, 95% CI: 0.155–0.634, P = 0.001) showed a negative causal relationship with osteosarcoma. The supplementary analysis methods (MR-Egger, weighted median, simple mode, and weighted mode) consistently validated the direction and magnitude of these findings. The sensitivity analysis indicated that the data were reliable and free from bias. Conclusion Using the Mendelian randomization approach, this study suggest that GCST90274776, GCST90274822, and GCST90274847 may be risk factors for osteosarcoma, whereas GCST90274844 appears to exhibit a protective effect against the disease.
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spelling doaj-art-eda8b2bb0e524263846d22e7242bee302025-08-20T04:03:02ZengSpringerDiscover Oncology2730-60112025-07-0116111410.1007/s12672-025-03283-8Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcomaHong Tang0Na Tang1Yueling Liao2Tao Tan3Hui Xie4Jiong Wang5Xie Hui6Department of Spine surgery, Affiliated Hospital (Clinical College) of Xiangnan UniversityDepartment of Cardiovascular medicine, Affiliated Hospital (Clinical College) of Xiangnan UniversityDepartment of Nusing, Affiliated Hospital (Clinical College) of Xiangnan UniversityFaculty of Applied Sciences, Macao Polytechnic UniversityFaculty of Applied Sciences, Macao Polytechnic UniversityDepartment of Spine surgery, Affiliated Hospital (Clinical College) of Xiangnan UniversityDepartment of Radiation Oncology, Affiliated Hospital (Clinical College) of Xiangnan UniversityAbstract Objective To investigate the causal relationship between 91 circulating inflammatory proteins and osteosarcoma using the two-sample Mendelian randomization method. Method Corresponding exposure and outcome data were extracted from genome-wide association study (GWAS) databases. A two-sample Mendelian randomization analysis was conducted on the data, with the inverse-variance weighted (IVW) method serving as the primary analytical approach. This was complemented by MR-Egger, weighted median, simple mode, and weighted mode methods to validate the results. Sensitivity analyses were also performed to verify the reliability of the data. Results The IVW analysis revealed a positive causal relationship between GCST90274776 (OR = 3.02, 95% CI: 0.033–0.117, P = 0.028), GCST90274822 (OR = 1.603, 95% CI: 1.014–2.535, P = 0.043), and GCST90274847 (OR = 2.580, 95% CI: 1.155–5.762, P = 0.021) and osteosarcoma. In contrast, GCST90274844 (OR = 0.313, 95% CI: 0.155–0.634, P = 0.001) showed a negative causal relationship with osteosarcoma. The supplementary analysis methods (MR-Egger, weighted median, simple mode, and weighted mode) consistently validated the direction and magnitude of these findings. The sensitivity analysis indicated that the data were reliable and free from bias. Conclusion Using the Mendelian randomization approach, this study suggest that GCST90274776, GCST90274822, and GCST90274847 may be risk factors for osteosarcoma, whereas GCST90274844 appears to exhibit a protective effect against the disease.https://doi.org/10.1007/s12672-025-03283-8Circulating inflammatory proteinsOsteosarcomaCausal associationTwo-sample mendelian randomization
spellingShingle Hong Tang
Na Tang
Yueling Liao
Tao Tan
Hui Xie
Jiong Wang
Xie Hui
Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma
Discover Oncology
Circulating inflammatory proteins
Osteosarcoma
Causal association
Two-sample mendelian randomization
title Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma
title_full Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma
title_fullStr Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma
title_full_unstemmed Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma
title_short Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma
title_sort two sample mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma
topic Circulating inflammatory proteins
Osteosarcoma
Causal association
Two-sample mendelian randomization
url https://doi.org/10.1007/s12672-025-03283-8
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