Causal relationship between educational attainment and pancreatitis:a Mendelian randomization study
曹瑞奇 1冯正源 1吴佼星 1李杰 1王铮 1仵正 1周灿灿1
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作者信息
1. 西安交通大学第一附属医院肝胆外科,西安交通大学胰腺疾病诊疗中心,陕西西安 710061
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摘要
目的 通过孟德尔随机化(Mendelian randomization,MR)分析探究受教育程度(educational attainment,EA)与胰腺炎之间的因果关系.方法 采用双样本MR分析,EA和胰腺炎的全基因组关联研究(GWAS)汇总数据分别来自SSGAC数据库和FinnGen数据库R9版本.采用逆方差加权(inverse variance weighted,IVW)、MR-Egger和weighted median法探究EA与胰腺炎之间的因果关系.通过Cochran's Q检验和漏斗图等方法评估异质性和定向的水平多效性.结果 共有604个与EA相关的单核苷酸多态性(SNP)被纳入研究,EA与急性胰腺炎和慢性胰腺炎发病风险均具有明显的负相关性(急性胰腺炎:OR=0.52,95％CI:0.44～0.62,P=2.43×10-14;慢性胰腺炎:OR=0.51,95％CI:0.41～0.64,P=7.20×10-9).MR-Egger 和 weighted median 的结果也提示 EA 与胰腺炎发病风险呈负相关.敏感性分析结果表明研究没有违反MR的基本假设.结论 EA与急性、慢性胰腺炎的发生存在因果关系,EA与胰腺炎的发病风险呈负相关.
Abstract
Objective To explore the causal relationship between education level and pancreatitis risk through Mendelian randomization.Methods A two-sample Mendelian randomization analysis was conducted using genome-wide association study(GWAS)summary data.The GWAS data for education level and pancreatitis were obtained from SSGAC database and the FinnGen database(version R9).Causal relationship between education level and pancreatitis was explored using the inverse variance weighted(IVW),MR-Egger,and weighted median methods.Heterogeneity and directional pleiotropy were evaluated using Cochran's Q test and funnel plots.Results Totally 604 SNPs associated with education level were included.The results provided evidence that there was negative relationship between education level and pancreatitis risk.For acute pancreatitis,OR=0.52,95％CI:0.44-0.62,P=2.4 3 × 10-14 while for chronic pancreatitis,OR=0.51,95％CI:0.41-0.64,P=7.20 × 10-9.Results from MR-Egger and weighted median analyses obtained the same results.The results of sensitivity analysis indicated that this study did not violate the basic assumptions of Mendelian randomization.Conclusion There is a causal relationship between education level and the occurrence of pancreatitis.The educational level is negatively correlated with the risk of pancreatitis.
关键词
胰腺炎/受教育程度(EA)/孟德尔随机化(MR)/全基因组关联研究(GWAS)/风险因素
Key words
pancreatitis/educational attainment(EA)/Mendelian randomization(MR)/genome-wide association study(GWAS)/risk factor
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