The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study
ObjectiveTo explore the influence of serum metabolites on the risk of psoriasis.MethodsIn the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance W...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343301/full |
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| author | Yujie Yang Xuwei Zheng Haiying Lv Bin Tang Bin Tang Bin Tang Bin Tang Bin Tang Yiyuan Zhong Qianqian Luo Yang Bi Kexin Yang Haixin Zhong Haiming Chen Haiming Chen Haiming Chen Haiming Chen Haiming Chen Chuanjian Lu Chuanjian Lu Chuanjian Lu Chuanjian Lu Chuanjian Lu |
| author_facet | Yujie Yang Xuwei Zheng Haiying Lv Bin Tang Bin Tang Bin Tang Bin Tang Bin Tang Yiyuan Zhong Qianqian Luo Yang Bi Kexin Yang Haixin Zhong Haiming Chen Haiming Chen Haiming Chen Haiming Chen Haiming Chen Chuanjian Lu Chuanjian Lu Chuanjian Lu Chuanjian Lu Chuanjian Lu |
| author_sort | Yujie Yang |
| collection | DOAJ |
| description | ObjectiveTo explore the influence of serum metabolites on the risk of psoriasis.MethodsIn the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio’s odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran’s Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages.ResultsIn the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism.ConclusionCirculating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment. |
| format | Article |
| id | doaj-art-f932fc8a491546c8a03711c91341ba02 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-f932fc8a491546c8a03711c91341ba022025-01-03T14:19:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13433011343301The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis studyYujie Yang0Xuwei Zheng1Haiying Lv2Bin Tang3Bin Tang4Bin Tang5Bin Tang6Bin Tang7Yiyuan Zhong8Qianqian Luo9Yang Bi10Kexin Yang11Haixin Zhong12Haiming Chen13Haiming Chen14Haiming Chen15Haiming Chen16Haiming Chen17Chuanjian Lu18Chuanjian Lu19Chuanjian Lu20Chuanjian Lu21Chuanjian Lu22The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, ChinaGuangdong Provincial Clinical Medicine Research Center for Chinese Medicine Dermatology, Guangzhou, ChinaGuangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, ChinaGuangdong Provincial Clinical Medicine Research Center for Chinese Medicine Dermatology, Guangzhou, ChinaGuangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, ChinaGuangdong Provincial Clinical Medicine Research Center for Chinese Medicine Dermatology, Guangzhou, ChinaGuangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, ChinaObjectiveTo explore the influence of serum metabolites on the risk of psoriasis.MethodsIn the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio’s odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran’s Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages.ResultsIn the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism.ConclusionCirculating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343301/fullpsoriasisMendelian randomizationmetabolitescausal effectimplication |
| spellingShingle | Yujie Yang Xuwei Zheng Haiying Lv Bin Tang Bin Tang Bin Tang Bin Tang Bin Tang Yiyuan Zhong Qianqian Luo Yang Bi Kexin Yang Haixin Zhong Haiming Chen Haiming Chen Haiming Chen Haiming Chen Haiming Chen Chuanjian Lu Chuanjian Lu Chuanjian Lu Chuanjian Lu Chuanjian Lu The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study Frontiers in Immunology psoriasis Mendelian randomization metabolites causal effect implication |
| title | The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study |
| title_full | The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study |
| title_fullStr | The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study |
| title_full_unstemmed | The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study |
| title_short | The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study |
| title_sort | causal relationship between serum metabolites and the risk of psoriasis a mendelian randomization and meta analysis study |
| topic | psoriasis Mendelian randomization metabolites causal effect implication |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343301/full |
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