首页|孟德尔随机化探索维生素B12缺乏性贫血和1型糖尿病风险的因果关系

孟德尔随机化探索维生素B12缺乏性贫血和1型糖尿病风险的因果关系

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
目的 使用孟德尔随机化(Mendelian randomization,MR)研究方法确定维生素B12(VitB12)缺乏性贫血是否与1型糖尿病(type 1 diabetes,T1D)有因果关系.方法 双样本MR研究选择从T1D和VitB12缺乏性贫血的全基因组关联研究获得的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,采用逆方差加权(inverse-variance weighted,IVW)作为MR的主要分析方法,并额外采用加权中位数法(weighted median,WME)、MR-Egger和weighted mode方法来进行验证.对工具变量进行敏感性分析,保证分析的稳健性.结果 共获得10个与VitB12缺乏性贫血密切相关的SNP作为工具变量,IVW结果(OR=2.706,95％CI 1.357～5.396,P＜0.05)、WME 结果(OR=5.179,95％CI 2.678～10.015,P＜0.05)、MR-Egger 结果(OR=13.088,95％CI 2.230～76.802,P＜0.05)和 Weighted mode 结果(OR=5.699,95％CI 2.807～11.570,P＜0.05)均表明基因预测VitB12缺乏性贫血与T1D的发病风险显著相关.同时反向MR研究发现T1D并不是VitB12缺乏性贫血原因.多种敏感性分析表明研究分析结果具有稳健性.结论 本研究表明VitB12缺乏性贫血是T1D发生的危险因素,两者之间存在正向因果关联.
Causal relationship between vitamin B12 deficiency anemia and risk of type 1 diabetes mellitus by Mendelian randomization analysis
Objective To determine whether vitamin B12(VitB12)deficiency anemia is causally associated with type 1 diabetes(T1D)by Mendelian randomization analysis(MR).Methods From genome-wide association studies,the independent single nucleotide pol-ymorphisms(SNP)closely associated with T1D and VitB12 deficiency anemia were selected as instrumental variables.Inverse-variance weighting(IVW)was used for MR analysis,and additional weighted median(WME),MR-Egger,and weighted mode methods were used to validate the results.Sensitivity analyses of instrumental variables were performed to ensure the robustness of the analysis.Results Total of 10 SNPs strongly associated with VitB12 deficiency anemia were obtained as instrumental variables.I VW(OR=2.706,95％CI 1.357-5.396,P＜0.05),WME(OR=5.179,95％CI 2.678-10.015,P＜0.05),MR-Egger(OR=13.088,95％CI2.230-76.802,P＜0.05),and weighted mode(OR=5.699,95％CI 2.807～11.570,P＜0.05)results showed that the gene prediction of VitB12 deficiency anemia was significantly associated with the risk of T1D.Meanwhile the reverse MR study showed that T1D was not the cause of VitB12 deficiency anemia.Sensitivity analysis supported the reliability of the study findings.Conclusion This study sug-gests that VitB12 deficiency anemia is a risk factor for T1D,and there is a positive causal correlation between them.

Mendelian randomizationvitamin B12 deficiency anemiatype 1 diabetessingle nucleotide polymorphismcausal inference

赵晨玥、高景波、郭荣、曹桂芝、郭敏、岳昊、薛慧琴

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山西医科大学儿科医学系,太原 030001

山西省儿童医院,山西省妇幼保健院细胞遗传室

孟德尔随机化 维生素B12缺乏性贫血 1型糖尿病 单核苷酸多态性 因果推断

山西省回国留学人员科研项目山西省"四个一批"科技兴医创新计划山西省儿童医院博士基金山西省卫生健康委科研项目

2023-1802021SY242019482023016

2024

10.13753/j.issn.1007-6611.2024.05.015

山西医科大学学报
山西医科大学

山西医科大学学报

CSTPCD
影响因子：0.931
ISSN：1007-6611
年,卷(期)：2024.55(5)
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