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CC BY 4.0 · Glob Med Genet 2024; 11(01): 48-58
DOI: 10.1055/s-0044-1779665
Original Article

Identification of Novel Risk Variants of Inflammatory Factors Related to Myeloproliferative Neoplasm: A Bidirectional Mendelian Randomization Study

Yang Li    *
1   State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, People's Republic of China
2   Tianjin Institutes of Health Science, Tianjin, People's Republic of China
,
Ting Sun    *
1   State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, People's Republic of China
2   Tianjin Institutes of Health Science, Tianjin, People's Republic of China
,
Jia Chen    *
1   State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, People's Republic of China
2   Tianjin Institutes of Health Science, Tianjin, People's Republic of China
,
Lei Zhang 
1   State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, People's Republic of China
2   Tianjin Institutes of Health Science, Tianjin, People's Republic of China
3   School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
› Author Affiliations Funding Information This work was supported by grants from the National Natural Science Foundation of China (82270152, 81970121, 82100151), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-2-003, 2021-I2M-1-073, 2023-I2M-QJ-015, 2021-I2M-1-003), and Clinical Research Fund of National Center for Clinical Medical Research of Hematology Diseases (2023NCRCA0109).
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Abstract

Epidemiological and experimental evidence has linked chronic inflammation to the etiology of myeloproliferative neoplasm (MPN). However, it remains unclear whether genetic associations with specific inflammatory biomarkers are causal or due to bias. This study aimed to assess the effect of C-reactive protein (CRP) and systemic inflammatory regulators on MPN within a bidirectional Mendelian randomization design. Genetic associations with MPN were derived from a publicly available genome-wide association study (GWAS) comprising 1,086 cases and 407,155 controls of European ancestry. Additionally, data on inflammation were extracted from two GWASs focusing on CRP and cytokines. The causal relationships between exposure and outcome were explored using the inverse variance weighted (IVW) method. To confirm the final results, multiple sensitivity analyses, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were simultaneously employed. Our results suggest that lower levels of macrophage-migration inhibitory factor (IVW estimate odds ratio [OR IVW] per SD genetic cytokines change: 0.641; 95% confidence interval [CI]: 0.427–0.964; p = 0.032) and higher levels of interleukin-2 receptor α (lL2Rα, 1.377, 95% CI: 1.006–1.883; p = 0.046) are associated with an increased risk of MPN. Genetically predicted MPN is related to increased levels of RANTES (IVW estimate β: 0.043, 95% CI: 0.002–0.084; p = 0.039) and interleukin-10 (IVW estimate β: 0.030, 95% CI: 0.001–0.060; p = 0.041). This study provides evidence for a causal relationship between CRP, systemic inflammatory regulators, and MPN, and new insights into the etiology, prevention, and prognosis of MPN.

Keywords

myeloproliferative neoplasms - inflammatory regulators - bidirectional Mendelian randomization

Data Availability Statement

All data used in the current study are publicly available GWAS summary data.


Ethics Approval Statement

This study utilized publicly available data from participant studies that had already received ethical approval from a committee responsible for human experimentation. No additional ethical approval was necessary for this particular study.


Authors' Contributions

L.Z. designed the research, was the principal investigator, and took primary responsibility for the paper. Y.L. wrote the main manuscript text. T.S. and J.C. edited the article.


* Yang Li, Ting Sun, and Jia Chen contributed equally to this study and should be regarded as co-first authors.


Supplementary Material



Publication History

Article published online:
12 February 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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