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    系统性红斑狼疮与急性胰腺炎因果关系的孟德尔随机化研究

    Mendelian randomization study on causal relationship between systemic lupus erythematosus and acute pancreatitis

    • 摘要: 目的 本研究旨在运用两样本孟德尔随机化(MR)分析,探究系统性红斑狼疮(SLE)与急性胰腺炎(AP)发病风险之间的关系。方法 获取SLE和AP的全基因组关联研究(GWAS)数据,以单核苷酸多态性(SNPs)作为工具变量(IVs),筛选敏感SNPs进行分析。借助逆方差加权法(IVW)和加权中位数法(WM)进行MR分析,通过优势比(OR)评估SLE与AP的因果关系,并对结果进行敏感性检验。结果 最终纳入9个SNPs位点作为IVs,随机效应模型下IVW法和WM法估计的OR值分别为1.089(95% CI:1.047~1.133,P<0.001)和1.079(95% CI:1.025~1.136,P=0.004),明确SLE与AP存在正向因果关系。Cochran's Q检验显示,纳入分析SNPs无显著异质性(P>0.05)。MR-Egger回归方程截距项为-0.016(P=0.355),表明结果不受基因水平多效性的影响。留一法分析和漏斗图进一步验证结果稳定可靠。结论 SLE与AP存在正向因果关系,SLE患者患AP的风险显著增高。

       

      Abstract: Objective To explore the relationship between systemic lupus erythematosus (SLE) and the risk of acute pancreatitis (AP) using two-sample Mendelian randomization (MR) analysis.Methods Genome-wide association study (GWAS) data for SLE and AP were obtained. Sensitive SNPs were selected for analysis, using single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, MR analysis was conducted using inverse variance weighted (IVW) and weighted median (WM) methods, and the odds ratio (OR) was calculated to evaluate the causal relationship between SLE and AP. The results were validated through sensitivity analysis.Results A total of 9 SNPs loci were included as IVs. Under the random effects model, the OR values estimated by IVW and WM methods were 1.089 (95%CI:1.047-1.133, P<0.001) and 1.079 (95%CI:1.025-1.136, P=0.004), respectively, indicating a positive causal relationship between SLE and AP. Cochran's Q test showed no significant heterogeneity among the included SNPs (P>0.05). The MR-Egger regression intercept was -0.016 (P=0.355), suggesting that the results were not affected by pleiotropy at the genetic level. Leave-one-out analysis and funnel plots further confirmed the stability and reliability of the results.Conclusions There is a positive causal relationship between SLE and AP, and SLE patients present a significantly higher risk of developing AP.

       

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