{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:07:51Z","timestamp":1787850471580,"version":"build-2784847793"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Postherpetic neuralgia (PHN) is a debilitating complication of herpes zoster, characterized by persistent neuropathic pain that significantly impairs patients\u2019 quality of life. Identifying factors that determine PHN susceptibility is crucial for its management. Interleukin-18 (IL-18), a pro-inflammatory cytokine implicated in chronic pain, may play a critical role in PHN development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we conducted bidirectional two-sample Mendelian randomization (MR) analyses to assess genetic relationships and potential causal associations between IL-18 protein levels increasing and PHN risk, utilizing genome-wide association study (GWAS) datasets on these traits. Two IL-18 datasets obtained from the EMBL\u2019s European Bioinformatics Institute database which contained 21,758 individuals with 13,102,515 SNPs and Complete GWAS summary data on IL-18 protein levels which contained 3,394 individuals with 5,270,646 SNPs. The PHN dataset obtained from FinnGen biobank had 195,191 individuals with 16,380,406 SNPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings from two different datasets of IL-18 protein levels suggest a correlation between genetically predicted elevations in IL-18 protein levels and an increased susceptibility to PHN.(IVW, OR and 95% CI: 2.26, 1.07 to 4.78; p = 0.03 and 2.15, 1.10 to 4.19; p =0.03, respectively), potentially indicating a causal effect of IL-18 protein levels increasing on PHN risk. However, we did not detect any causal effect of genetic liability to PHN risk on IL-18 protein levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest new insights into identifying IL-18 protein levels increasing at risk of developing PHN and may aid in the development of novel prevention and treatment approaches for PHN.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1183378","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T04:12:14Z","timestamp":1684987934000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia 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