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双样本双向孟德尔随机化法分析人免疫细胞与增生性瘢痕之间的因果关系

吴虹林 陈咏菲 李舒婷 杨浩 李晓卉 唐冰 朱家源 胡志成

吴虹林, 陈咏菲, 李舒婷, 等. 双样本双向孟德尔随机化法分析人免疫细胞与增生性瘢痕之间的因果关系[J]. 中华烧伤与创面修复杂志, 2024, 40(6): 572-578. DOI: 10.3760/cma.j.cn501225-20240203-00046.
引用本文: 吴虹林, 陈咏菲, 李舒婷, 等. 双样本双向孟德尔随机化法分析人免疫细胞与增生性瘢痕之间的因果关系[J]. 中华烧伤与创面修复杂志, 2024, 40(6): 572-578. DOI: 10.3760/cma.j.cn501225-20240203-00046.
Wu HL,Chen YF,Li ST,et al.Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method[J].Chin J Burns Wounds,2024,40(6):572-578.DOI: 10.3760/cma.j.cn501225-20240203-00046.
Citation: Wu HL,Chen YF,Li ST,et al.Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method[J].Chin J Burns Wounds,2024,40(6):572-578.DOI: 10.3760/cma.j.cn501225-20240203-00046.

双样本双向孟德尔随机化法分析人免疫细胞与增生性瘢痕之间的因果关系

doi: 10.3760/cma.j.cn501225-20240203-00046
基金项目: 

国家自然科学基金面上项目 82172213

详细信息
    通讯作者:

    胡志成,Email:huzhch5@mail.sysu.edu.cn

Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method

Funds: 

General Program of National Natural Science Foundation of China 82172213

More Information
  • 摘要:   目的  运用双样本双向孟德尔随机化法,探讨人免疫细胞与增生性瘢痕(HS)之间的因果关系。  方法  该研究基于双样本双向孟德尔随机化(MR)法,分别从全基因组关联分析catalog数据库和FinnGen数据库获取731种人免疫细胞与HS的数据集。设置显著阈值,筛选与免疫细胞及HS显著相关的单核苷酸多态性(SNP)并排除弱工具变量偏倚的影响。采用逆方差加权(IVW)法[同时采用错误发现率(FDR)中的Benjamini-Hochberg法校正其P值]初步检测免疫细胞与HS的因果关系并筛选与HS有显著因果关系的免疫细胞。进一步地,采用双样本MR分析的5种方法:IVW法、加权中位数法、简单模式法、加权模式法和MR-Egger法绘制散布图检测筛选出的免疫细胞与HS的因果关系。针对符合假设的免疫细胞SNP,进行Cochran Q检验评估异质性,进行MR-Egger回归和MR-PRESSO法排除水平多效性,进行留一法分析来评估显著结果是否由单个SNP决定。采用双样本MR分析中IVW法反向检测HS与免疫细胞之间的因果关系。  结果  731种免疫细胞达到显著阈值的SNP数量从7个到1 786个不等,HS中达到显著阈值的SNP数量有119个,这些SNP的F值均>10,提示具有弱工具变量偏倚的可能性较小。IVW法分析显示,60种免疫细胞与HS具有潜在因果关系(P值均<0.05),经Benjamini-Hochberg法校正后,仅CD45RA和CD39双阳性调节性T细胞(Treg)与HS具有潜在因果关系(PFDR<0.05)。IVW法(比值比为1.16,95%置信区间为1.08~1.24,P<0.05、PFDR<0.05)、加权中位数法(比值比为1.16,95%置信区间为1.05~1.28,P<0.05)、加权模式法(比值比为1.14,95%置信区间为1.02~1.27,P<0.05)和MR-Egger 法(比值比为1.18,95%置信区间为1.07~1.30,P<0.05)的散布图均显示,CD45RA和CD39双阳性Treg的14个SNP与HS患病风险存在因果关系;仅简单模式法的散布图显示,CD45RA和CD39双阳性Treg的14个SNP与HS患病风险的因果关系不明显(P>0.05)。Cochran Q检验显示,CD45RA和CD39双阳性Treg与HS的因果关系不存在异质性(P>0.05)。MR-Egger回归、MR-PRESSO法分析显示,CD45RA和CD39双阳性Treg与HS的显著因果关系不存在水平多效性(P>0.05)。留一法分析显示,CD45RA和CD39双阳性Treg与HS的显著因果关系在逐个剔除SNP后结果稳定。双样本反向MR分析显示,HS与731种免疫细胞均无潜在因果关系(P>0.05)。  结论  从遗传学的角度揭示,免疫细胞CD45RA和CD39双阳性Treg可能会增加HS患病风险。

     

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  • 1  人免疫细胞与增生性瘢痕的双样本双向孟德尔随机化分析假设图

    注:图中虚线表示2个因子之间不产生作用、实线表示2个因子之间可以产生作用;图中免疫细胞目前已知有731种

    2  逆方差加权法分析人免疫细胞与增生性瘢痕之间的因果关系

    注:FDR指错误发现率;P值为单纯逆方差加权法的所得值,PFDR 值为经Benjamini-Hochberg法校正后的逆方差加权法所得值;红色箭头指CD45RA和CD39双阳性调节性T细胞;每个条柱对应一种免疫细胞

    3  双样本孟德尔随机化法分析人免疫细胞CD45RA和CD39双阳性调节性T细胞的14个 SNP与增生性瘢痕因果关系的散布图

    注:SNP为单核苷酸多态性;直线的斜率表示每种方法的因果关联,斜率为正值表明该免疫细胞可增加增生性瘢痕的发生风险

    4  留一法分析人免疫细胞CD45RA和CD39双阳性调节性T细胞的14个SNP与增生性瘢痕之间的因果关系

    注:SNP为单核苷酸多态性;线段中的圆点为比值比,误差线均在0的右侧,提示结果可靠

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  • 收稿日期:  2024-02-03

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