{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":54,"searchCount":0},"additional":{"submitter":["Kang X"],"funding":["Barts Charity","Medical Research Council"],"pagination":["e1672-e1679"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8032365"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["96(12)"],"pubmed_abstract":["<h4>Objective</h4>To evaluate the effects of long-term tumor necrosis factor (TNF) inhibition on the risk and age at onset of Parkinson disease (PD), we performed a 2-sample Mendelian randomization study using genome-wide association studies (GWAS) summary statistics.<h4>Methods</h4>Genetic variants in the vicinity of <i>TNFRSF1A</i>, the gene encoding TNF receptor 1 (TNFR1), were identified as predictive of pharmacologic blockade of TNFR1 signaling by anti-TNF therapy, based on genetic associations with lower circulating C-reactive protein (CRP; GWAS n = 204,402). The effects of TNF-TNFR1 inhibition were estimated for PD risk (n<sub>cases</sub>/<sub>controls</sub> = 37,688/981,372) and age at PD onset (n = 28,568) using GWAS data from the International Parkinson's Disease Genomics Consortium and 23andMe, Inc. To validate variants as proxies of long-term anti-TNF treatment, we also assessed whether variant associations reflected anticipated effects of TNFR1 inhibition on Crohn disease, ulcerative colitis, and multiple sclerosis risk (n = 38,589-45,975).<h4>Results</h4>TNF-TNFR1 signaling inhibition was not estimated to affect PD risk (odds ratio [OR] per 10% lower circulating CRP = 0.99; 95% confidence interval [CI] 0.91-1.08) or age at onset (0.13 years later onset; 95% CI -0.66 to 0.92). In contrast, genetically indexed TNF-TNFR1 signaling blockade predicted reduced risk of Crohn disease (OR 0.75; 95% CI 0.65-0.86) and ulcerative colitis (OR 0.84; 95% CI 0.74-0.97) and increased multiple sclerosis risk (OR 1.57; 95% CI 1.36-1.81). Findings were consistent across models using different genetic instruments and Mendelian randomization estimators.<h4>Conclusions</h4>Our findings do not imply that TNF-TNFR1 signaling inhibition will prevent or delay PD onset.<h4>Classification of evidence</h4>This study provides Class II evidence that TNF-TNFR1 signaling inhibition is not associated with the risk or age at onset of PD."],"journal":["Neurology"],"pubmed_title":["Tumor Necrosis Factor Inhibition and Parkinson Disease: A Mendelian Randomization Study."],"pmcid":["PMC8032365"],"funding_grant_id":["MGU0364","MC_UU_00019/2"],"pubmed_authors":["Kang X","Noyce AJ","Williams DM","Pedersen NL","Bandres-Ciga S","Wirdefeldt K","Ploner A"],"view_count":["54"],"additional_accession":[]},"is_claimable":false,"name":"Tumor Necrosis Factor Inhibition and Parkinson Disease: A Mendelian Randomization Study.","description":"<h4>Objective</h4>To evaluate the effects of long-term tumor necrosis factor (TNF) inhibition on the risk and age at onset of Parkinson disease (PD), we performed a 2-sample Mendelian randomization study using genome-wide association studies (GWAS) summary statistics.<h4>Methods</h4>Genetic variants in the vicinity of <i>TNFRSF1A</i>, the gene encoding TNF receptor 1 (TNFR1), were identified as predictive of pharmacologic blockade of TNFR1 signaling by anti-TNF therapy, based on genetic associations with lower circulating C-reactive protein (CRP; GWAS n = 204,402). The effects of TNF-TNFR1 inhibition were estimated for PD risk (n<sub>cases</sub>/<sub>controls</sub> = 37,688/981,372) and age at PD onset (n = 28,568) using GWAS data from the International Parkinson's Disease Genomics Consortium and 23andMe, Inc. To validate variants as proxies of long-term anti-TNF treatment, we also assessed whether variant associations reflected anticipated effects of TNFR1 inhibition on Crohn disease, ulcerative colitis, and multiple sclerosis risk (n = 38,589-45,975).<h4>Results</h4>TNF-TNFR1 signaling inhibition was not estimated to affect PD risk (odds ratio [OR] per 10% lower circulating CRP = 0.99; 95% confidence interval [CI] 0.91-1.08) or age at onset (0.13 years later onset; 95% CI -0.66 to 0.92). In contrast, genetically indexed TNF-TNFR1 signaling blockade predicted reduced risk of Crohn disease (OR 0.75; 95% CI 0.65-0.86) and ulcerative colitis (OR 0.84; 95% CI 0.74-0.97) and increased multiple sclerosis risk (OR 1.57; 95% CI 1.36-1.81). Findings were consistent across models using different genetic instruments and Mendelian randomization estimators.<h4>Conclusions</h4>Our findings do not imply that TNF-TNFR1 signaling inhibition will prevent or delay PD onset.<h4>Classification of evidence</h4>This study provides Class II evidence that TNF-TNFR1 signaling inhibition is not associated with the risk or age at onset of PD.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2024-10-19T12:06:02.69Z","creation":"2022-02-11T14:15:05.948Z"},"accession":"S-EPMC8032365","cross_references":{"pubmed":["33608417"],"doi":["10.1212/WNL.0000000000011630"]}}