ArticleNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2020
Mendelian randomization study to evaluate the effects of interleukin-6 signaling on four neurodegenerative diseases.
Article in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Relationships between accelerometer-measured and multiple sclerosis: a 2-sample Mendelian randomization study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Does the Single Nucleotide Polymorphism rs2228145 in IL6R Truly Reflect IL-6 Signaling in Mendelian Randomization Studies?Immune network · 2025Article
- Genetically predicted associations between circulating cytokines and autoimmune diseases: a bidirectional two-sample Mendelian randomization.Frontiers in immunology · 2024Article
- Associations of the circulating levels of cytokines with risk of amyotrophic lateral sclerosis: a Mendelian randomization study.BMC medicine · 2023Article
- A review of Mendelian randomization in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2022Review
- Association Between C-Reactive Protein and Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.Frontiers in genetics · 2022Article
- Body Mass Index, Interleukin-6 Signaling and Multiple Sclerosis: A Mendelian Randomization Study.Frontiers in immunology · 2022Article
- Anti-IL-6 therapies in central nervous system inflammatory demyelinating diseases.Frontiers in immunology · 2022Review
- Effect of plasma vitamin C levels on Parkinson's disease and age at onset: a Mendelian randomization study.Journal of translational medicine · 2021Article
- Educational Attainment and Ischemic Stroke: A Mendelian Randomization Study.Frontiers in genetics · 2021Article
- Joint Analysis of Genome-Wide Association Data Reveals No Genetic Correlations Between Low Back Pain and Neurodegenerative Diseases.Frontiers in genetics · 2021Article
- Growth Differentiation Factor 15 Is Associated With Alzheimer's Disease Risk.Frontiers in genetics · 2021Article
- Circulating Interleukins and Risk of Multiple Sclerosis: A Mendelian Randomization Study.Frontiers in immunology · 2021Article
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4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple sclerosis (MS) is a complex neurological disease and chronic inflammatory disease. Until now, observational studies have reported positive association between serum interleukin-6 (IL-6) levels and MS risk. In order to develop effective therapies, we should establish the causal link between IL-6 signaling and MS. However, it is currently unknown whether IL-6 signaling is causally associated with the risk of MS.
methodsHere, we selected the increased soluble IL-6R (s-IL-6R) levels as the indirect markers for reduced IL-6 signaling, and performed a Mendelian randomization (MR) study using the rs2228145 variant as the instrumental variable to evaluate and quantify the effect of IL-6 signaling on the risk of MS. To be a comparison, we also evaluated the causal association of IL-6 signaling with the risk of other three neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).
resultsWe found that the increased s-IL-6R levels (per 1 standard deviation) were significantly associated with decreased MS risk (OR = 0.96, 95% CI 0.94-0.98, P = 1.69E-04), but not associated with the risk of AD (OR = 1.01, 95% CI 0.92-1.11, P = 0.835), PD (OR = 0.94, 95% CI 0.84-1.05, P = 0.261), or ALS (OR = 1.00, 95% CI 0.92-1.10, P = 0.9411).
conclusionOur findings have the similar directional effects to an existing humanized anti-IL-6R monoclonal antibody Tocilizumab which could bind to the IL-6 binding site of human IL-6R and competitively inhibit IL-6 signaling. Hence, we provided genetic evidence that inhibiting the IL-6 signaling such as tocilizumab treatment might represent a novel therapy for MS.
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