Category: Epidemiology
Objective: To evaluate whether inhibition of Tumor Necrosis Factor (TNF) signaling may reduce the risk of Parkinson’s disease (PD) and/or delay onset of PD.
Background: Anti-TNF therapeutic use is associated with reduced PD risk among inflammatory bowel disease patients, which may imply TNF inhibition confers neuroprotection. We examined whether there is support for this hypothesis in a Mendelian randomization (MR) framework.
Method: We indexed the effects of long-term blockade of TNF signaling on PD risk and age at onset using a MR study design. Genetic variants in the vicinity of TNFRSF1A, the gene encoding TNF receptor 1, were identified as indexing TNF blockade based on associations with circulating C-reactive protein (CRP) in large-scale genome wide association studies (GWAS; N=204,402). GWAS of PD risk (37,688 cases, 981,372 controls) and age at onset (N=28,568) were used to evaluate the associations of TNF-inhibiting variation with these traits. Primary MR models were based on the use of a sentinel variant (rs1800693) with suggested functional relevance for TNFR1 signaling and strong evidence for association with CRP (P=9E-08). To improve the power to detect associations, we also performed secondary MR models using a larger region of variants in TNFRSF1A weighted consistently by the variants’ associations with CRP. Both analytical approaches were also applied to GWAS of Crohn’s disease (CD; 12,194 cases, 28,072 controls) and ulcerative colitis risk (UC; 12,366 cases, 33,609 controls) as positive controls to validate our strategy.
Results: There were no associations between rs1800693 and PD risk (Odds ratio=1.00 per TNF-inhibiting allele; 95% CI: 0.98, 1.02) or age at onset (0.05 years per allele; 95% CI: -0.13, 0.24). In contrast, the same variant was associated with lower risk of CD and UC. Findings did not differ in secondary MR models.
Conclusion: Our findings do not support the notion that exposure to TNF inhibitors will prevent or delay PD onset among the general population.
To cite this abstract in AMA style:
X. Kang, A. Ploner, N. Pedersen, J. Ludvigsson, S. Bandres-Ciga, A. Noyce, K. Wirdefeldt, D. Williams. Predicting the effects of Tumor Necrosis Factor inhibition on the risk and age at onset of Parkinson’s disease: A Mendelian randomization study [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/predicting-the-effects-of-tumor-necrosis-factor-inhibition-on-the-risk-and-age-at-onset-of-parkinsons-disease-a-mendelian-randomization-study/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/predicting-the-effects-of-tumor-necrosis-factor-inhibition-on-the-risk-and-age-at-onset-of-parkinsons-disease-a-mendelian-randomization-study/