鉴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。
Identifying the genetic association between systemic lupus erythematosus and the risk of autoimmune liver diseases.
机构信息
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Department of Rehabilitation Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
出版信息
J Autoimmun. 2024 May;145:103188. doi: 10.1016/j.jaut.2024.103188. Epub 2024 Mar 7.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
背景
既往关于系统性红斑狼疮（SLE）与自身免疫性肝病（AILDs）之间关系的研究结果并不一致。因此，我们采用孟德尔随机化（MR）方法来探究 SLE 与 AILDs 之间的因果关联。
方法
采用两样本 MR 分析，使用源自全基因组关联研究（GWAS）数据集的汇总统计数据。进一步通过几种敏感性分析对逆方差加权（IVW）、MR-Egger 和加权中位数（WM）进行了支持。
结果
我们检测到 SLE 与原发性胆汁性胆管炎（PBC）（比值比（OR）=1.31，95%置信区间（CI）=1.15-1.51，P<0.01；调整后的 OR=1.63，95%CI=1.39-1.90，P<0.01）和原发性硬化性胆管炎（PSC）（OR=1.09，95%CI=1.01-1.08，P=0.03；调整后的 OR=1.10，95%CI=1.00-1.21，P=0.04）之间存在因果遗传关联。但在 SLE 与自身免疫性肝炎之间未发现因果关联。
结论
我们首次采用 MR 分析来探究 SLE 与各种 AILDs 之间的因果关系，结果表明 SLE 患者发生 PBC 和 PSC 的风险增加。
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