两样本孟德尔随机化分析饮酒频率和心血管疾病发病风险之间的关系

Two-sample Mendelian randomization analysis of the relationship between drinking frequency and the risk of cardiovascular disease

目的应用孟德尔随机化(MR)的方法分析饮酒频率与心血管疾病的相关性。方法从UKBiobank和FinnGen数据库中获取饮酒频率和心血管疾病的全基因组关联分析(GWAS)数据,从UKBiobank数据库中饮酒频率的GWAS汇总数据得出与饮酒频率独立相关的单核苷酸多态性(SNPs)作为工具变量,应用工具变量及固定效应反方差加权(IVW)、MR-Egger和Weighted median分析饮酒频率与心血管疾病的相关性。结果共筛选出99个SNPs与饮酒频率相关。IVW结果显示,饮酒频率增高会导致心衰和高血压的发病风险增加(P=0.004、0.018);饮酒频率每增加1次,心衰的发病风险增加1.234倍[比值比(OR)(95%CI)=1.234(1.071~1.422)],高血压的发病风险增加1.191倍[OR(95%CI)=1.191(1.030~1.376)];饮酒频率与冠心病发病风险无因果关系[P=0.977,OR(95%CI)=0.997(0.797~1.247)]。MR-Egger回归结果表明研究结果无水平多效性(P>0.05)。结论饮酒频率和心衰及高血压存在因果关系。

Objective To analyze the correlation between drinking frequency and cardiovascular disease by Mendelian randomization(MR).Methods Genome wide association study(GWAS)data of drinking frequency and cardiovascular disease were obtained from the UKBiobank and FinnGen databases.Single nucleotide polymorphisms(SNPs)independently associated with drinking frequency were obtained as instrumental variables from the GWAS summary data of drinking frequency in the UKBiobank database.The correlation between drinking frequency and cardiovascular disease was analyzed by instrumental variables and fixed-effects inverse-variance-weighted(IVW),MR-Egger and Weighted median.Results A total of 99 SNPs were screened to be associated with drinking frequency.The results of IVW showed that an increased in drinking frequency leads to an increased the risk of heart failure and hypertension(P=0.004,0.018);for every increase in drinking frequency,the risk of heart failure increased by 1.234 times[odds ratios(OR)(95%CI)=1.234(1.071-1.422)],and the risk of hypertension increased by 1.191 times[OR(95%CI)=1.191(1.030-1.376)];there was no causal relationship between drinking frequency and risk of coronary heart disease[P=0.977,OR(95%CI)=0.997(0.797-1.247)].The results of MR-Egger regression showed that there was no horizontal pleiotropy in the study(P>0.05).Conclusion There is a causal relationship between drinking frequency and heart failure and hypertension.