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22-04-2024 | Aplastic Anemia | Original Article

Mendelian randomization of circulating proteome identifies IFN-γ as a druggable target in aplastic anemia

Authors: Shanshan Qin, Yingxin Jiang, Yang Ou, Yanxia Zhan, Lili Ji, Pengcheng Xu, Xia Shao, Hao Chen, Tong Chen, Yunfeng Cheng

Published in: Annals of Hematology

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Abstract

Background

Aplastic anemia (AA) is a kind of bone marrow failure (BMF) characterized by pancytopenia with hypoplasia/aplasia of bone marrow. Immunosuppressive therapy and bone marrow transplantation are effective methods to treat severe aplastic anemia. However, the efficacy is limited by complications and the availability of suitable donors. This study aimed to determine whether any circulating druggable protein levels may have causal effects on AA and provide potential novel drug targets for AA.

Methods

Genetic variants strongly associated with circulating druggable protein levels to perform Mendelian randomization (MR) analyses were used. The effect of these druggable protein levels on AA risk was measured using the summary statistics from a large-scale proteomic genome-wide association study (GWAS) and FinnGen database (https://​www.​finngen.​fi/​en/​access_​results). Multivariable MR analyses were performed to statistically adjust for potential confounders, including platelet counts, reticulocyte counts, neutrophil counts, and proportions of hematopoietic stem cells.

Results

The data showed that higher level of circulating IFN-γ levels was causally associated with AA susceptibility. The causal effects of circulating IFN-γ levels on the AA were broadly consistent, when adjusted for platelet counts, reticulocyte counts, neutrophil counts and proportions of hematopoietic stem cells.

Conclusions

High levels of circulating IFN-γ levels might increase the risk of AA and might provide a potential novel target for AA.
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Metadata
Title
Mendelian randomization of circulating proteome identifies IFN-γ as a druggable target in aplastic anemia
Authors
Shanshan Qin
Yingxin Jiang
Yang Ou
Yanxia Zhan
Lili Ji
Pengcheng Xu
Xia Shao
Hao Chen
Tong Chen
Yunfeng Cheng
Publication date
22-04-2024
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-024-05746-4
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