发育医学电子杂志2024,Vol.12Issue(6) :415-421.DOI:10.3969/j.issn.2095-5340.2024.06.002

系统性红斑狼疮与子痫前期因果关系的孟德尔随机化分析

Mendelian randomization analysis on the causal relationship between systemic lupus erythematosus and preeclampsia

桂琦 侯伟 胡甲琳 姜淑芳 游艳琴 卢彦平
发育医学电子杂志2024,Vol.12Issue(6) :415-421.DOI:10.3969/j.issn.2095-5340.2024.06.002

系统性红斑狼疮与子痫前期因果关系的孟德尔随机化分析

Mendelian randomization analysis on the causal relationship between systemic lupus erythematosus and preeclampsia

桂琦 1侯伟 1胡甲琳 2姜淑芳 3游艳琴 3卢彦平4
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作者信息

  • 1. 解放军医学院,北京 100853
  • 2. 南开大学医学院,天津 300071
  • 3. 解放军总医院第一医学中心 妇产科,北京 100853
  • 4. 解放军总医院第七医学中心 妇产医学部,北京100700
  • 折叠

摘要

目的 探究系统性红斑狼疮(systemic lupus erythematosus,SLE)与子痫前期(preeclampsia,PE)之间的因果关系.方法 通过R包TwoSampleMR(v 0.6.4)从IEU OpenGWAS数据库中筛选与SLE具有显著差异的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,共获取包含7071163个SNP的SLE数据集和包含24165538个SNP的PE数据集.采用逆方差加权(inverse-variance weighting,IVW)法、孟德尔随机化(Mendelian randomization,MR)-Egger回归法、加权中位数(weighted median estimator,WME)法、简单模式(simple mode,SM)、加权模式(weighted mode,WM)进行MR分析,通过计算优势比(odds ratio,OR)值和95%CI评价SLE和PE之间的因果关系,并进行Cochran's Q异质性检验、MR-Egger回归水平多效性检验和留一法评估验证数据的稳定性和可靠性.结果 共纳入42个SNP作为工具变量.IVW分析提示SLE与PE发病风险之间存在因果关系(OR=1.038,95%CI:1.003~1.073,P<0.05),MR-Egger分析也提示SLE与PE之间存在因果关系(OR=1.094,95%CI:1.020~1.174,P<0.05),在WME、SM及WM分析中未发现两者存在因果关系.Cochran's Q异质性检验和MR-Egger水平多效性检验显示,SNP之间不存在异质性及水平多效性.留一法检验提示没有单个SNP对整体结果有较大影响.结论 MR分析提示SLE可增加PE的发病风险.

Abstract

Objective To investigate the causal relationship between systemic lupus erythematosus (SLE) and preeclampsia (PE).Method Utilizing the R package TwoSampleMR (0.6.4),single nucleotide polymorphism (SNP) significantly associated with SLE were screened from the IEU OpenGWAS database and used as instrumental variables.A dataset containing 7071163 SNP for SLE and another with 24165538 SNP for PE were obtained.Mendelian randomization (MR) analysis were conducted using inverse-variance weighting (IVW),MR-Egger regression,the weighted median estimator (WME),simple mode (SM),and weighted mode (WM).The causal relationship between SLE and PE was evaluated by calculating odds ratios (OR) and 95% CI.Cochran's Q test for heterogeneity,MR-Egger horizontal pleiotropy test and leave-one-out analysis were performed to assess the stability and reliability of the data.Result A total of 42 SNP were included as instrumental variables.The IVW analysis suggested a causal relationship between SLE and the risk of PE (OR=1.038,95% CI:1.003-1.073,P<0.05).Consistent results were also obtained from the MR-Egger regression analysis (OR=1.094,95% CI:1.020-1.174,P<0.05).However,no causal relationship was found between SLE and PE in the WME,SM,and WM analysis.Cochran's Q test for heterogeneity and MR-Egger horizontal pleiotropy test indicated no heterogeneity or horizontal pleiotropy among the SNP.The leave-one-out analysis suggested that no single SNP had a significant impact on the overall results.Conclusion MR analysis suggests that SLE may increase the risk of developing PE.

关键词

孟德尔随机化/系统性红斑狼疮/子痫前期/全基因组关联分析/单核苷酸多态性

Key words

Mendelian randomization/Systemic lupus erythematosus/Preeclampsia/Genome-wide association study/Single nucleotide polymorphism

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出版年

2024
发育医学电子杂志
人民卫生出版社

发育医学电子杂志

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影响因子:0.212
ISSN:2095-5340
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