他汀类药物与1型或2型糖尿病的因果关系:一项两样本孟德尔随机化研究
Causal associations between statins and type 1 or type 2 diabetes:a two-sample mendelian randomization study
翁丽燕 1翁金燕 1徐靖1
作者信息
- 1. 丽水市中心医院药学部(浙江丽水 323000)
- 折叠
摘要
目的 利用孟德尔随机化(MR)分析他汀类药物分别与1型糖尿病、2型糖尿病之间的因果关系.方法 基于全基因组关联研究(GWAS)汇总数据,选择相互独立且与他汀类药物及糖尿病高度相关的单核苷酸多态性(SNP)作为工具变量.运用MR-Egger法、加权中位数法、逆方差加权(IVW)法、简单模式法和加权模式法进行两样本MR分析,评估他汀类药物分别与1型或2型糖尿病之间的因果关系,并进行异质性检验、多效性分析以及敏感性分析以评价研究的可靠性.结果 在全基因组显著性水平(P＜5 × 10-8)上,共纳入78个独立与他汀类药物相关的SNPs作为工具变量.IVW分析结果显示,他汀类药物与1型糖尿病风险增加存在因果关系[OR=1.524,95％CI(1.077,2.157),P=0.017],与2型糖尿病风险增加同样存在因果关系[OR=1.261,95％CI(1.165,1.366),P＜0.001].研究结果均不受多效性、异质性的影响,敏感性分析结果验证了结果的可靠性.结论 他汀类药物可能是增加1型或2型糖尿病风险的危险因素,但仍需更大样本量的GWAS数据进一步深入研究以验证该因果关系.
Abstract
Objective To analyze the causal relationship between statins and type 1 or type 2 diabetes mellitus by using Mendelian randomization(MR).Methods Based on the collected data of genome-wide association studies(GWAS),single nucleotide polymorphism(SNP),which were independent of each other and highly correlated with statins and diabetes mellitus,were selected as tool variables.MR-Egger regression,weighted median,inverse variance weighting(IVW),simple mode and weighted mode were used for two-sample MR analyses to evaluate the causal relationship between statins and type 1 or type 2 diabetes respectively,and heterogeneity tests,multiplicity analyses,and sensitivity analysis to evaluate the reliability of the study.Results A total of 78 SNPs independently associated with statins were included as tool variables in this study at the genome-wide significance level(P＜5×10-8).The results of IVW analysis showed that statins were causally associated with an increased risk of type 1 diabetes mellitus(OR=1.524,95％CI 1.077 to 2.157,P=0.017),and there was also a causal relationship between statins and the increased risk of type 2 diabetes(OR=1.261,95％CI 1.165 to 1.366,P＜0.001).The results were not affected by multiplicity and heterogeneity,and the reliability of the results was verified by sensitivity analysis.Conclusion Statins may be a risk factor for increasing the risk of type 1 or type 2 diabetes.However,further studies with larger sample sizes of GWAS data are still needed to verify the causal association.
关键词
他汀类药物/1型糖尿病/2型糖尿病/因果关系/孟德尔随机化/全基因组关联研究Key words
Statins/Type 1 diabetes/Type 2 diabetes/Causality/Mendelian randomization/Genome-wide association study引用本文复制引用
出版年
2024
NETL
NSTL
万方数据