AUTHOR=Lu Hui , Wu Peng-Fei , Zhang Wan , Liao Xiaoyao 

TITLE=Circulating Interleukins and Risk of Multiple Sclerosis: A Mendelian Randomization Study

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.647588

DOI=10.3389/fimmu.2021.647588

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Previous research have implicated critical roles of systemic inflammation in the development of Multiple Sclerosis (MS). But the causal relationship between interleukins (ILs) and MS has not been fully elucidated.</p></sec><sec><title>Objective</title><p>In this study, we applied Mendelian randomization (MR) approaches to address the causal associations between genetically determined circulating levels of ILs and the risk of MS.</p></sec><sec><title>Methods</title><p>Genetic instruments for circulating IL-1 receptor antagonist (IL-1Ra), IL-2 receptor α subunit (IL-2Rα), IL-6, IL-16, IL-17, and IL-18 were obtained from recently published genome-wide association studies (GWAS). Summary-level data for MS were obtained from the International Multiple Sclerosis Genetics Consortium. MR analyses were performed using the R software (version 3.6.1, The R Foundation) and the TwoSampleMR package.</p></sec><sec><title>Results</title><p>Genetic predisposition to higher circulating levels of IL-2Rα were significantly associated with MS risk. The odds ratio (OR) was 1.22 (95% confidence interval [CI], 1.12–1.32; <italic>p</italic> &lt; 0.001) per one standard deviation increase in circulating IL-2Rα levels. There was a suggestive association of circulating IL-1Ra with MS risk (OR, 0.94; 95% CI, 0.88–0.99; <italic>p</italic> = 0.027). The other ILs were not associated with the outcome.</p></sec><sec><title>Conclusion</title><p>Our results indicated that circulating IL-2Rα was causally associated with risk of MS.</p></sec>