Circulating inflammatory proteins and risk of Parkinson’s disease and other neurodegenerative disorders: a two-sample Mendelian randomization study

Abstract

Background: Accumulating studies have suggested associations between peripheral inflammation and neurodegenerative disorders, including Parkinson's disease (PD). Objective: To evaluate the causal associations between 91 plasma inflammatory proteins and 4 neurodegenerative disorders. Methods: Two-sample Mendelian randomization studies were performed using summary statistics extracted from genome-wide association studies of 91 plasma inflammatory proteins and 4 neurodegenerative disorders. Results: Genetically proxied tumor necrosis factor receptor superfamily member 9 levels were causally associated with reduced risk of PD (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.74-0.92, p = 4.18 x 10-4, Bonferroni-corrected p < 0.05 for 91 proteins). Additionally, we identified potential causal associations between the levels of C-C motif chemokine 20 (OR = 1.14, 95%CI = 1.03-1.25, p = 1.29 x 10-2) and Alzheimer's disease, between levels of leukemia inhibitory factor receptor (OR = 0.91, 95%CI = 0.84-0.98, p = 1.12 x 10-2) and tumor necrosis factor-β (OR = 0.95, 95%CI = 0.93-0.98, p = 1.01 x 10-3) and amyotrophic lateral sclerosis, between levels of adenosine deaminase (OR = 0.81, 95%CI = 0.71-0.94, p = 5.14 x 10-3) and interleukin-18 (OR = 0.81, 95%CI = 0.69-0.96, p = 1.68 x 10-2) and multiple sclerosis. Conclusions: Our study unveils plausible causal associations between circulating inflammatory factors and risk of 4 neurodegenerative disorders. These findings hold promise for promoting risk assessment and prevention of neurodegenerative disorders, meriting further exploration.