.png){kind=icon}
.png){kind=icon}
Return
Genetically predicted CXCL16 expression is associated with Parkinson’s disease risk and peripheral immune cell dysregulation: a two-sample mendelian randomization study
.png){kind=icon}
OA
AI
Z
R
H
M
DOI：10.1186/s13041-026-01324-z.png)
.png){kind=icon}
.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Parkinson’s disease (PD) is a progressive neurodegenerative disorder with limited disease-modifying therapies. PANoptosis, an integrated form of programmed cell death involving apoptosis, pyroptosis, and necroptosis, has been implicated in neuroinflammation-related neurodegeneration. However, the roles of PANoptosis-related genes in PD remain unclear. We performed two-sample Mendelian randomization (MR) using cis-eQTL instruments from the eQTLGen Consortium for 30 PANoptosis-related genes, with PD GWAS data from Nalls et al. 2019 as the outcome. Instrumental variables were selected using a hierarchical strategy, with genome-wide significant cis-eQTLs as primary instruments and a relaxed threshold applied only for genes with fewer than three independent SNPs. Sensitivity analyses included MR-Egger, weighted median, MR-PRESSO, MR-RAPS, and leave-one-out analyses. SMR/HEIDI testing and two-step MR mediation using 731 peripheral immune traits were also performed. Genetically predicted higher CXCL16 expression was associated with increased PD risk (OR = 1.115, 95% CI 1.060–1.173, p = 2.4 × 10−5), while higher FADD expression was associated with reduced PD risk (OR = 0.861, 95% CI 0.790–0.939, p = 7.1 × 10−4). CASP1 and IFI27 were nominally significant and considered exploratory. Sensitivity analyses were directionally consistent, although MR-Egger estimates were imprecise. SMR/HEIDI supported CXCL16. Exploratory mediation analysis identified 63/66 candidate immune mediators after FDR correction. These findings provide MR-based genetic evidence linking CXCL16 expression to PD risk, with exploratory mediation through peripheral immune phenotypes. The CXCL16–immune cell–PD axis warrants further experimental validation.
Keywords:
Parkinson’s disease
PANoptosis
Mendelian randomization
Immune cells
CXCL16
Neuroinflammation
eQTL
AI Summary
Key information extracted from the uploaded paper, including a brief overview, abstract, background, key highlights, visual analysis, and future outlook.
Journal
IF:
2.9
Papers:
1.6K
Citations:
4.5K
Organization
Cited Papers