Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk
BackgroundPostherpetic neuralgia (PHN) is a debilitating complication of herpes zoster, characterized by persistent neuropathic pain that significantly impairs patients’ quality of life. Identifying factors that determine PHN susceptibility is crucial for its management. Interleukin-18 (IL-18), a pr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183378/full |
| _version_ | 1797821044283670528 |
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| author | Xiao Liang Yuchao Fan |
| author_facet | Xiao Liang Yuchao Fan |
| author_sort | Xiao Liang |
| collection | DOAJ |
| description | BackgroundPostherpetic neuralgia (PHN) is a debilitating complication of herpes zoster, characterized by persistent neuropathic pain that significantly impairs patients’ 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.MethodsIn 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’s 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.ResultsOur 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.ConclusionThese 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. |
| first_indexed | 2024-03-13T09:46:57Z |
| format | Article |
| id | doaj.art-d84d9caed0ce4cebabeab432727024e5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T09:46:57Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d84d9caed0ce4cebabeab432727024e52023-05-25T04:12:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11833781183378Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia riskXiao Liang0Yuchao Fan1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Anesthesiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, ChinaBackgroundPostherpetic neuralgia (PHN) is a debilitating complication of herpes zoster, characterized by persistent neuropathic pain that significantly impairs patients’ 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.MethodsIn 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’s 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.ResultsOur 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.ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183378/fullpostherpetic neuralgiainterleukin-18bidirectional Mendelian randomizationgenome-wide association studyherpes zoster |
| spellingShingle | Xiao Liang Yuchao Fan Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk Frontiers in Immunology postherpetic neuralgia interleukin-18 bidirectional Mendelian randomization genome-wide association study herpes zoster |
| title | Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk |
| title_full | Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk |
| title_fullStr | Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk |
| title_full_unstemmed | Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk |
| title_short | Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk |
| title_sort | bidirectional two sample mendelian randomization analysis reveals a causal effect of interleukin 18 levels on postherpetic neuralgia risk |
| topic | postherpetic neuralgia interleukin-18 bidirectional Mendelian randomization genome-wide association study herpes zoster |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183378/full |
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