Effect of immune-related plasma proteins under genetic regulation on Parkinson's disease
Wang Zihao
Li Peishan
Xia Huan
Du Xinyu
Kelibinuer·Saidierding
Yang Xinling
Abstract：Objective To explore the connection between immune-related plasma proteins and Parkinson's disease.Methods By analyzing genome-wide association study data of 4907 immune-related plasma proteins,we assessed their direct impact on the risk of Parkinson's disease.Single-nucleus RNA sequencing data were also utilized for protein expression analysis.Results Four im-mune-related proteins,cerebral dopamine neurotrophic factor(CDNF),cathepsin B(CTSB),im-munoglobulin G Fc receptor 2a(FCGR2A),and hemoglobin beta subunit(HBB),were identified to be associated with the risk of Parkinson's disease.Among them,increased expression levels of CDNF,CTSB and HBB were found to decrease the risk(OR=0.871,95％CI:0.779-0.973,P=0.015;OR=0.835,95％CI:0.758-0.920,P=0.001;OR=0.735,95％CI:0.631-0.857,P=0.001),whereas increased level of FCGR2A was associated with a higher risk of PD(OR=1.137,95％CI:1.058-1.223,P=0.001).Singl e-cell sequencing analyzes protein expression and its dis-tribution among different cell types in the brain.CDNF and CTSB exhibit high expression levels in multiple brain cell types,FCGR2A is predominantly expressed in brain microglia and HBB shows minimal expression in the brain.Conclusion There are potential links between the four proteins CDNF,CTSB,FCGR2A and HBB and the risk of Parkinson's disease.Our results emphasize that the genetic risk variants of Parkinson's disease influence the disease's occurrence by modulating the expression of these immune-related proteins.Additionally,single-cell expression data reveal the expression patterns of these target proteins in the brain.
Keywords：Parkinson diseasecathepsin Bblood proteinscerebral dopamine neurotrophic factorhemoglobin beta subunitsingle-cell sequencingimmunoglobulin G Fc receptor 2a(FCGR2A)
Publication Date：2024-07-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 806-810 )