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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies have suggested an association between inflammatory markers and low back pain (LBP), but the causal relationship between these factors remains uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a bidirectional two-sample Mendelian randomization analysis (MR) study to investigate whether there is a causal relationship between inflammatory markers and low back pain. We obtained genetic data for CRP, along with its upstream inflammatory markers IL-6, IL-8, and IL-10, as well as low back pain from publicly available genome-wide association studies (GWAS). We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald Ratio, and MR-PRESSO, to test for causal relationships. Sensitivity analyses were also conducted to assess the robustness of the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analyses utilizing the Inverse Variance Weighted (IVW) method, the MR-Egger method, and the weighted median method indicated that IL-6 may be associated with an increased risk of LBP (Effect Size: -0.009, 95% Confidence Interval: -0.013\u20130.006, p = 9.16e-08); however, in the reverse direction, there was no significant causal effect of LBP on inflammatory markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study used a Mendelian randomization approach and found that elevated IL-6 levels may reduce the risk of LBP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1174656","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T13:28:43Z","timestamp":1689254923000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Assessing the causal relationship between genetically determined inflammatory biomarkers and low back pain risk: a bidirectional two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"14","author":[{"given":"Wenhan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunwen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caigui","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huahui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengguo","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"Disease","year":"2018","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5952165","article-title":"Review of animal models of intervertebral disc degeneration: pathophysiology, regeneration, and translation to the clinic","volume":"2016","author":"Daly","year":"2016","journal-title":"BioMed Res Int"},{"key":"B3","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrrheum.2013.160","article-title":"Role of cytokines in intervertebral disc degeneration: pain and disc content","volume":"10","author":"Risbud","year":"2014","journal-title":"Nat Rev Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.E.01273","article-title":"Lumbar disc disorders and low-back pain: socioeconomic factors and consequences","volume":"88","author":"Katz","year":"2006","journal-title":"J Bone Joint Surg Am"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1347299","article-title":"Inflammatory mediators in intervertebral disk degeneration and discogenic pain","volume":"3","author":"Wuertz","year":"2013","journal-title":"Global Spine J"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.027045","article-title":"Pain and high sensitivity C reactive protein in patients with chronic low back pain and acute sciatic pain","volume":"64","author":"St\u00fcrmer","year":"2005","journal-title":"Ann Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2005.11.005","article-title":"The course of high-sensitive C-reactive protein in correlation with pain and clinical function in patients with acute lumbosciatic pain and chronic low back pain - 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