干果摄入量与2型糖尿病因果关系的孟德尔随机化研究

Relationship Between Dried Fruit Intake and Type 2 Diabetes:a Mendelian Randomization Study

目的:利用两样本孟德尔随机化(MR)分析的方法探究干果摄入量(DFI)与2型糖尿病(T2DM)之间的因果关系。方法:DFI的全基因组关联分析(GWAS)数据来源于UK Biobank(421764例),作为本项MR研究的暴露;另从DIAGRAM联盟数据库中获取与T2DM相关的GWAS数据(898130例)作为结局的发现数据集。为了验证结果可靠性,在FINNGEN数据库中获取另一队列人群的T2DM GWAS数据(304769例)作为验证数据集。以上数据都来源于欧洲人群。主要采用逆方差加权法(IVW)、MR Egger法、加权中位数法(WME)、简单众数法(SM)和加权众数法(WM)5种方法进行MR分析,根据效应指标比(OR)和95%CI评估结果。结果:以IVW为主要分析方法的MR分析表明,DFI增加可降低T2DM的发生风险[IVW OR=0.434,95%CI(0.312,0.602)],其余4种方法所评估的效应方向与IVW一致。验证集数据分析结果再次证实了以上发现,在所有分析中未发现多效性的存在。结论:增加DFI与T2DM风险降低之间存在因果关系。

Objective:Two-sample Mendelian randomization(MR)analysis was used to investigate the relationship between dried fruit intake(DFI)and type 2 diabetes mellitus(T2DM).Methods:Genome-wide association analysis(GWAS)data for DFI(421764 cases)were obtained from UK Biobank as exposure for this MR study,and GWAS data(898130 cases)associated with T2DM were obtained from the DIAGRAM consortium database as a discovery dataset for outcomes.To verify the reliability of the results,the T2DM GWAS data(304769 cases)of another cohort population was obtained in the FINNGEN database as the replication dataset.All the above data were from European populations.The inverse variance-weighted method(IVW),MR Egger method,weighted median method(WME),simple mode method(SM),and weighted majority method(WM)were used for MR analysis,and the results were evaluated according to the effect index ratio(OR)and 95%CI.Results:MR analysis with IVW as the main analysis method showed that the increase of DFI could reduce the risk of T2DM(IVW OR=0.434,95%CI 0.312-0.602),and the direction of effect evaluated by the other four methods were consistent with that of IVW.The results of replication dataset analysis reaffirmed the above findings,and no pleiotropy was found in any of the analyses.Conclusion:There is relationship between higher DFI and a reduced risk of T2DM.