目的 探讨20种膳食习惯与2型糖尿病（type 2 diabetes,T2DM）之间的因果关系。方法 采用两样本孟德尔随机化方法(mendelian randomization,MR)，以20种膳食习惯为暴露因素，T2DM为结局因素，在全基因组关联研究（genome-wide association study,GWAS）选取与20种膳食习惯显著相关(P＜5.0×10-8)的单核苷酸多态性(single nucleotide polymorphisms,SNPs)作为工具变量。MR分析方法包括逆方差加权法（inverse variance weighted，IVW）、MR Egger回归、加权中位数法、加权模式法，其中IVW为最主要的方法。结果 IVW分析结果显示，乙醇摄入频率(OR：1.30,95%CI：1.14~1.49,P＜0.001)和咖啡摄入量(OR：1.48，95%CI：1.06~2.06，P=0.020)与T2DM发病风险增加有因果关系；而油性鱼摄入(OR：0.78，95%CI：0.62~0.98，P=0.029),奶酪摄入(OR：0.68，95%CI:0.56~0.82，P＜0.001) 与T2DM发病风险降低有因果关系。敏感性分析验证了研究结果的稳定性。结论 在欧洲人群中，基因预测的乙醇摄入频率,咖啡、油性鱼、奶酪摄入量与T2DM发病存在因果关系，其中乙醇摄入频率和咖啡摄入量可能是T2DM发病的危险因素；而油性鱼和奶酪摄入量可能是预防T2DM发生的保护因素。

Objective To investigate the causal relationship between 20 dietary habits and type 2 diabetes (T2DM).Methods A two-sample Mendelian randomization (MR) approach was employed,with 20 dietary habits as exposure factors and T2DM as the outcome.Single nucleotide polymorphisms (SNPs) significantly associated (P＜ 5.0×10-8) with the dietary habits were selected from genome-wide association studies (GWAS) as instrumental variables.MR analyses included inverse variance weighted (IVW),MR-Egger regression,weighted median,and weighted mode methods,with IVW being the primary method.Results IVW analysis revealed that alcohol intake frequency (OR:1.30,95%CI:1.14-1.49,P＜0.001) and coffee consumption (OR:1.48,95%CI:1.06-2.06,P=0.020) were causally associated with an increased risk of T2DM.Conversely,oily fish intake (OR:0.78,95%CI:0.62-0.98,P= 0.029) and cheese consumption (OR:0.68,95%CI:0.56-0.82,P＜0.001) were associated with a reduced risk of T2DM.Sensitivity analyses confirmed the stability of the findings.Conclusions In Europe, genetically predicted alcohol intake frequency,coffee consumption,oily fish intake,and cheese consumption exhibit causal relationships with T2DM incidence.Alcohol and coffee intake may be risk factors for T2DM,whereas oily fish and cheese intake may serve as protective factors against disease development.

R472.9

国家自然科学基金 (81904269)；福建省自然科学基金（2019J01358）