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. 2023 Dec 18;13(1):22543.
doi: 10.1038/s41598-023-49233-8.

Genetically predicted 486 blood metabolites concerning risk of systemic lupus erythematosus: a Mendelian randomization study

Li Zhao #  1 , Ruonan Wu #  2 , Zewen Wu #  3 , Xinling Liu  4 , Jingxuan Li  3 , Liyun Zhang  5 , Shuqiu Zhang  6
Affiliations

Genetically predicted 486 blood metabolites concerning risk of systemic lupus erythematosus: a Mendelian randomization study

Li Zhao et al. Sci Rep. .

Abstract

Metabolic abnormalities constitute a significant characteristic of systemic lupus erythematosus (SLE). We utilised a two-sample Mendelian randomisation (MR) study to evaluate the potential causal association between 486 blood metabolites and SLE. Exposure data at the metabolite level were extracted from 7824 European Genome-wide association studies (GWAS). Preliminary analysis utilised SLE GWAS data from FinnGen. The primary method for causal analysis relied on random inverse variance weighting (IVW). To ensure robustness, sensitivity analyses included the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Steiger testing and linkage disequilibrium score regression were employed to validate the identified metabolites. This study identified 12 metabolites, comprising six known chemical structures: 1,5-anhydroglucitol(1,5-AG) [odds ratio (OR) = 0.100, 95% confidence interval (CI): 0.015-0.773, P = 0.027), gamma-glutamylthreonine (OR = 0.077, 95% CI: 0.010-0.574, P = 0.012), 5-dodecenoate(12:1n7) (OR = 0.205, 95% CI: 0.061-0.685, P = 0.010), linoleoylglycerophosphoethanolamine * (OR = 0.159, 95% CI: 0.027-0.933, P = 0.044), erythrose (OR = 88.331,95% CI:1.098-63.214, P = 0.040) and 1-, adrenate (22:4n6) (OR = 9.876, 95% CI: 1.753-55.639, P = 0.001)]. Additionally, we found associations between SLE and six unknown chemical structures: X-06351 (OR = 0.071, 95% CI: 0.006-0.817, P = 0.034), X-10810 (OR = 4.268 95% CI: 1.260-14.459, P = 0.020), X-11412 (OR = 5.418 95% CI: 1.068-27.487, P = 0.041), X-11905 (OR = 0.551, 95%CI: 0.304-0.997, P = 0.049), X-12038 (OR = 0.178 95%CI: 0.032-0.988, P = 0.045), X-12217 (OR = 0.174 95%CI: 0.044-0.680, P = 0.014). This study offers evidence supporting a causal relationship between SLE and 12 circulating metabolites, six of which have known chemical structures and six that remain unidentified. These findings introduce a new perspective for further exploration of SLE mechanisms.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Workflow of the MR analysis.
Figure 2
Figure 2
Significant results for the IVW analysis.
Figure 3
Figure 3
Scatter plots of the MR analysis.
Figure 4
Figure 4
Leave-one-out results.
See this image and copyright information in PMC

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References

    1. Zucchi D, Elefante E, Schilirò D, Signorini V, Trentin F, Bortoluzzi A, Tani C. One year in review 2022: Systemic lupus erythematosus. Clin. Exp. Rheumatol. 2022 doi: 10.55563/clinexprheumatol/nolysy. - DOI - PubMed
    1. Xu Q, Ni JJ, Han BX, Yan SS, Wei XT, Feng GJ, Zhang H, Zhang L, Li B, Pei YF. Causal relationship between gut microbiota and autoimmune diseases: A two-sample Mendelian randomization study. Front. Immunol. 2022 doi: 10.3389/fimmu.2021.746998. - DOI - PMC - PubMed
    1. Xiang M, Wang Y, Gao Z, Wang J, Chen Q, Sun Z, Liang J, Xu J. Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization. Front. Immunol. 2023 doi: 10.3389/fimmu.2022.985729. - DOI - PMC - PubMed
    1. UPLC–MS/MS‐based plasma lipidomics reveal a distinctive signature in systemic lupus erythematosus patients-Chen-2021-MedComm-Wiley Online Library. 10.1002/mco2.67 Accessed 12 Aug 2023 (2023). - PMC - PubMed
    1. Zhang Q, Li X, Yin X, Wang H, Fu C, Wang H, Li K, Li Y, Zhang X, Liang H, Li K, Li H, Qiu Y. Metabolomic profiling reveals serum l-pyroglutamic acid as a potential diagnostic biomarker for systemic lupus erythematosus. Rheumatol. Oxf. Engl. 2021 doi: 10.1093/rheumatology/keaa126. - DOI - PubMed