Mendelian randomization of circulating proteome identifies IFN-γ as a druggable target in aplastic anemia.
Ann Hematol
; 103(7): 2245-2256, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38644415
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interferon-gamma
/
Proteome
/
Genome-Wide Association Study
/
Mendelian Randomization Analysis
/
Anemia, Aplastic
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Ann Hematol
Journal subject:
HEMATOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China