轮班工作与心脑血管疾病的孟德尔随机化研究  

Shift and cardiovascular and cerebrovascular diseases:Mendelian randomized study

作　　者：安洪鑫 夏侯鸾达 李云权 李伟 AN Hong-xin;XIAHOU Luan-da;LI Yun-quan;LI Wei(Department of Cardiology,The Affiliated Hospital of Guizhou Medical University,Guiyang,Guizhou 550004,China)

机构地区：[1]贵州医科大学附属医院心血管内科,贵州贵阳550004

出　　处：《现代预防医学》2024年第13期2305-2311,共7页Modern Preventive Medicine

基　　金：国家自然科学基金(82160086,81960047)。

摘　　要：目的使用孟德尔随机化(Mendelian randomization,MR)方法评估轮班工作(shift work)与心脑血管疾病(cardiovascular and cerebrovascular diseases,CCVD)的因果关系。方法从英国生物样本库(UK biobank,UKBB)及欧洲血统最大的全基因组关联研究(GWAS)提取轮班和9个CCVD的汇总统计数据用于MR分析,并使用FinnGen生物库重复分析进行验证,之后进一步使用meta分析合并发现队列和复制队列以扩大样本量来获得更可靠的因果效应。同时,使用两步MR方法评估CCVD相关危险因素对轮班工作和CCVD之间因果效应的潜在中介作用。多种敏感性分析方法验证结果的可靠性。结果这项研究基于IVW方法显示轮班工作会增加心血管疾病(cardiovascular disease,CVD)(OR=1.06,95%CI:1.02~1.10,FDR=0.003)、冠心病(coronary heart disease)(OR=1.32,95%CI:1.10~1.60,FDR=0.007)、心肌梗死(myocardial infarction)(OR=1.64,95%CI:1.24~2.20,FDR=0.003)和心绞痛(angina pectoris)(OR=1.40,95%CI:1.15~1.70,FDR=0.003)的发病风险。水平多效性效应(MR-Egger截距和MR-PRESSO全局检验的P值均>0.05)对结果产生偏差的可能性较小。此外,原发性高血压(essential hypertension,EHT)、2型糖尿病(type 2 diabetes,T2DM)、身体质量指数(body mass index,BMI)、抑郁状态、当前吸烟部分介导了轮班工作对CVD、冠心病、心肌梗死及心绞痛的因果效应,其中BMI对CVD、冠心病、心肌梗死的调节比分别为81.7%、47.03%、45.04%;EHT对冠心病、心肌梗死、心绞痛的调节比分别为42.87%、40.72%、57.05%;T2DM对CVD、冠心病、心肌梗死、心绞痛的调节比分别为12.51%、7.58%、5.27%、8.39%;抑郁状态对CVD、冠心病、心肌梗死、心绞痛的调节比分别为237.12%、26.00%、22.06%、32.60%;当前吸烟对CVD的调节比为11.42%。结论这项MR研究提供了可靠的证据支持轮班工作增加CVD、冠心病、心肌梗死及心绞痛的发病风险,EHT、T2DM、BMI、抑郁状态及当前吸烟部分介导了这种作用�Objective To evaluate the causal relationship between shift work(SW)and cardiovascular and cerebrovascular diseases(CCVD)by Mendelian randomized method.Methods The summary statistical data of shift and 9 CCVDs were extracted from UK biobank(UKBB)and the largest genome-wide association study(GWAS)of European descendants for MR analysis,and verified by data of FinnGen biological bank.After that,meta-analysis was used to combine discovery cohort and replication cohort to expand the sample size to obtain more reliable causal effects.At the same time,a two-step MR method was used to evaluate the potential mediating effect of CCVD-related risk factors on causal effects between shifts and CCVD.A variety of sensitivity analysis methods were used to verify the reliability of the results.Results This study showed that shifts increased risk of cardiovascular disease(CVD)(OR=1.06,95%CI:1.02-1.10,FDR=0.003),coronary heart disease(CHD)(OR=1.32,95%CI:1.10-1.60,FDR=0.007),myocardial infarction(MI)(OR=1.64,95%CI:1.24-2.20,FDR=0.003),and angina pectoris(AP)(OR=1.40,95%CI:1.15-1.70,FDR=0.003)based on the inverse-variance weighted(IVW)method.Pleiotropy test results(MR-Egger intercept and MR-PRESSO global test P>0.05)showed the robustness of results.In addition,essential hypertension(EHT),type 2 diabetes(T2DM),body mass index(BMI),depressive state(DS),and current smoking(CM)partially mediated the causal effects of shift on CVD,CHD,MI,and AP.And the proportions were as follows:[BMI:CVD(81.70%),CHD(47.03%),MI(45.04%)],[EHT:CHD(42.87%),MI(40.72%),AP(57.05%)],[T2DM:CVD(12.51%),CHD(7.58%),MI(5.27%),AP(8.39%)],[DS:CVD(237.12%),CHD(26.00%),MI(22.06%),AP(32.60%)],and[CM:CVD(11.42%)].Conclusion This study provides reliable evidence that shifts increase the risk of cardiovascular disease,coronary heart disease,myocardial infarction,and angina pectoris,which are partially mediated by essential hypertension,type 2 diabetes,BMI,depression and current smoking.

关 键 词：孟德尔随机化 轮班工作 心脑血管疾病 因果关系 

分 类 号：R743[医药卫生—神经病学与精神病学]