ArticleMolecular brain2026
Genetically predicted CXCL16 expression is associated with Parkinson's disease risk and peripheral immune cell dysregulation: a two-sample mendelian randomization study.
Article in Molecular brain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundParkinson'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.
methodsWe 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.
resultsGenetically predicted higher CXCL16 expression was associated with increased PD risk (OR = 1.115, 95% CI 1.060-1.173, p = 2.4 × 10
conclusionThese 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.
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