School of Pharmacy, Shanxi Medical University, Taiyuan, 030600, China.
School of Public Health, Shanxi Medical University, Taiyuan, 030001, China.
Sci Rep. 2023 Dec 18;13(1):22543. doi: 10.1038/s41598-023-49233-8.
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.
代谢异常是系统性红斑狼疮（SLE）的一个重要特征。我们利用两样本孟德尔随机化（MR）研究来评估 486 种血液代谢物与 SLE 之间潜在的因果关系。代谢物水平的暴露数据来自于 7824 项欧洲全基因组关联研究（GWAS）中提取。初步分析利用了 FinnGen 的 SLE GWAS 数据。因果分析的主要方法依赖于随机逆方差加权（IVW）。为了确保稳健性，敏感性分析包括 Cochran Q 检验、MR-Egger 截距检验、MR-PRESSO 和单样本剔除分析。Steiger 检验和连锁不平衡得分回归用于验证鉴定出的代谢物。这项研究确定了 12 种代谢物，其中包括 6 种已知的化学结构：1,5-脱水葡萄糖醇（1,5-AG）[比值比（OR）=0.100，95%置信区间（CI）：0.015-0.773，P=0.027]、γ-谷氨酰基苏氨酸（OR=0.077，95%CI：0.010-0.574，P=0.012）、5-十二碳烯酸（12:1n7）（OR=0.205，95%CI：0.061-0.685，P=0.010）、亚油酰基甘油磷酸乙醇胺*（OR=0.159，95%CI：0.027-0.933，P=0.044）、赤藓糖（OR=88.331，95%CI：1.098-63.214，P=0.040）和 1-，丙酸盐（22:4n6）（OR=9.876，95%CI：1.753-55.639，P=0.001）]。此外，我们还发现 SLE 与 6 种未知化学结构之间存在关联：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）。这项研究提供了证据支持 SLE 与 12 种循环代谢物之间存在因果关系，其中 6 种具有已知的化学结构，6 种尚未确定。这些发现为进一步探索 SLE 机制提供了新的视角。
