Previous studies on the relationship between systemic lupus erythematosus (SLE) and autoimmune liver diseases (AILDs) are inconclusive. Therefore, we employed Mendelian randomization (MR) to explore the causal associations between SLE and AILDs. A two-sample MR analysis was performed using summary-level statistics sourced from genome-wide association study (GWAS) datasets. Inverse-variance weighting (IVW), MR‒Egger, and weighted median (WM) were further supported by several sensitivity analyses. We detected causal genetic associations between SLE and primary biliary cholangitis (PBC) (odds ratio (OR) = 1.31, 95% CI = 1.15–1.51, P < 0.01; adjusted OR = 1.63, 95% CI = 1.39–1.90, P < 0.01) and between SLE and primary sclerosing cholangitis (PSC) (OR = 1.09, 95% CI = 1.01–1.08, P = 0.03; adjusted OR = 1.10, 95% CI = 1.00–1.21, P = 0.04). No causal association was found between SLE and autoimmune hepatitis. We are the first to use MR analysis to explore the causal relationships between SLE and various AILDs, revealing an increased risk of PBC and PSC in individuals with SLE.

中文翻译：

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确定系统性红斑狼疮与自身免疫性肝病风险之间的遗传关联

先前关于系统性红斑狼疮（SLE）与自身免疫性肝病（AILD）之间关系的研究尚无定论。因此，我们采用孟德尔随机化 (MR) 来探讨 SLE 和 AILD 之间的因果关系。使用来自全基因组关联研究 (GWAS) 数据集的汇总级统计数据进行了两个样本的 MR 分析。逆方差加权 (IVW)、MR-Egger 和加权中位数 (WM) 得到了多项敏感性分析的进一步支持。我们检测到 SLE 与原发性胆汁性胆管炎 (PBC) 之间存在因果遗传关联（比值比 (OR) = 1.31，95% CI = 1.15–1.51，P < 0.01；调整后 OR = 1.63，95% CI = 1.39–1.90，P < 0.01）以及 SLE 和原发性硬化性胆管炎 (PSC) 之间的差异（OR = 1.09，95% CI = 1.01–1.08，P = 0.03；调整后 OR = 1.10，95% CI = 1.00–1.21，P = 0.04）。没有发现系统性红斑狼疮和自身免疫性肝炎之间存在因果关系。我们率先使用 MR 分析来探索 SLE 与各种 AILD 之间的因果关系，揭示 SLE 患者发生 PBC 和 PSC 的风险增加。