摘要
目的采用双样本孟德尔随机化(MR)分析方法探讨糖脂代谢以及肥胖相关指标与心肌梗死的因果关联。方法从全基因组关联研究数据库中获取与表型相关的单核苷酸多态性(SNP)信息。其中体重指数和糖化血红蛋白数据包含99998个样本和8126035个SNP;腰臀比数据包含224459个样本和2562516个SNP;腰围和臀围数据包含462166个样本和9851867个SNP;空腹血糖数据包含24925个样本和约1200万个SNP;低密度脂蛋白胆固醇(LDL-C)数据包含201678个样本和12321875个SNP;高密度脂蛋白胆固醇(HDL-C)和甘油三酯数据包含156109个样本和15784414个SNP;体脂百分比、全身脂肪质量、躯干脂肪百分比和躯干脂肪质量数据包含454588个样本和9851867个SNP。本研究以逆方差加权法分析结果为主,分析各暴露因素与结局之间的关联。同时采用异质性检验(Cochran′s Q检验)分析SNP间的统计学异质性,采用MR多效性检验(MR-Egger法)分析SNP的水平多效性。采用多变量MR方法校正体重指数,再次验证各暴露因素与心肌梗死风险之间的关联。结果较高的体重指数(OR=1.070,95%CI 1.041~1.100)、腰臀比(OR=1.366,95%CI 1.113~1.677)、LDL-C(OR=1.638,95%CI 1.488~1.803)、甘油三酯(OR=1.445,95%CI 1.300~1.606)、腰围(OR=1.841,95%CI 1.650~2.055)、臀围(OR=1.247,95%CI 1.132~1.372)、体脂百分比(OR=1.795,95%CI 1.568~2.055)、全身脂肪质量(OR=1.519,95%CI 1.381~1.670)、躯干脂肪百分比(OR=1.538,95%CI 1.374~1.723)和躯干脂肪质量(OR=1.421,95%CI 1.294~1.561),以及较低的HDL-C(OR=0.799,95%CI 0.729~0.875)对心肌梗死具有因果效应(P均<0.05)。校正体重指数后,臀围、躯干脂肪百分比和躯干脂肪质量不再与心肌梗死相关;而腰臀比(OR=1.457,95%CI 1.132~1.877)、空腹血糖(OR=1.191,95%CI 1.024~1.383)、糖化血红蛋白(OR=1.129,95%CI 1.034~1.233)、LDL-C(OR=1.592,95%CI 1.314~1.929)、甘油三酯(OR=1.410,95%CI 1.279~1.553)、腰围(OR=1.922,95%CI 1.448~2.551)、体脂百分比(OR=1.421,95%CI 1.072~1.884)和全身脂肪质量(OR=1.295,95%CI 1.031~1.626)与心肌梗死呈正相关,HDL-C(OR=0.809,95%CI 0.729~0.897)与心肌梗死呈负相关。结论腹部肥胖和糖脂代谢紊乱是心肌梗死的危险因素。对糖脂代谢(空腹血糖、HDL-C、LDL-C、甘油三酯)及肥胖相关指标(腰围、腰臀比、体脂百分比和全身脂肪质量)进行筛查对于心肌梗死一级预防具有重大意义。
Objective To explore the causal association of glucose-lipid metabolism and obesity indicators with myocardial infarction by a two-sample Mendelian randomization analysis.Methods Single nucleotide polymorphisms(SNPs)related to phenotypes were obtained from genome-wide association study databases.The body mass index(BMI)and glycated hemoglobin dataset includes 99998 samples and 8126035 SNPs;the waist-to-hip ratio dataset includes 224459 samples and 2562516 SNPs;the waist circumference and hip circumference dataset includes 462166 samples and 9851867 SNPs;the fasting glucose dataset includes approximately 12 million SNPs;the low-density lipoprotein cholesterol(LDL-C)dataset includes 201678 samples and 12321875 SNPs;the high-density lipoprotein cholesterol(HDL-C),and triglycerides dataset includes 156109 samples and 15784414 SNPs;and the body fat percentage,whole-body fat mass,trunk fat percentage,and trunk fat mass dataset includes 454588 samples and 9851867 SNPs.This study primarily used inverse-variance weighted method to analyze the associations between various exposure factors and outcomes.Heterogeneity among SNPs was assessed using Cochran′s Q test,and horizontal pleiotropy of SNPs was examined using the MR-Egger method.Additionally,a multivariable MR approach was used to adjust for BMI,further validating associations between exposure factors and the risk of myocardial infarction.Results Higher BMI(OR=1.070,95%CI:1.041-1.100),waist-to-hip ratio(OR=1.366,95%CI:1.113-1.677),LDL-C(OR=1.638,95%CI:1.488-1.803),triglycerides(OR=1.445,95%CI:1.300-1.606),waist circumference(OR=1.841,95%CI:1.650-2.055),hip circumference(OR=1.247,95%CI:1.132-1.372),body fat percentage(OR=1.795,95%CI:1.568-2.055),whole-body fat mass(OR=1.519,95%CI:1.381-1.670),trunk fat percentage(OR=1.538,95%CI:1.374-1.723),and trunk fat mass(OR=1.421,95%CI:1.294-1.561),as well as lower HDL-C(OR=0.799,95%CI:0.729-0.875),have causal effects on myocardial infarction(all P<0.05).After adjusting for BMI,hip circumference,trunk fat percentage,and trunk fat mass were no longer associated with myocardial infarction.However,waist-to-hip ratio(OR=1.457,95%CI:1.132-1.877),fasting glucose(OR=1.191,95%CI:1.024-1.383),glycated hemoglobin(OR=1.129,95%CI:1.034-1.233),LDL-C(OR=1.592,95%CI:1.314-1.929),triglycerides(OR=1.410,95%CI:1.279-1.553),waist circumference(OR=1.922,95%CI:1.448-2.551),body fat percentage(OR=1.421,95%CI:1.072-1.884),and whole-body fat mass(OR=1.295,95%CI:1.031-1.626)remained positively associated with myocardial infarction,while HDL-C(OR=0.809,95%CI:0.729-0.897)remained negatively associated.Conclusions Abdominal obesity and dysregulation of glucose-lipid metabolism are risk factors for myocardial infarction.Screening for glucose-lipid metabolism(fasting glucose,HDL-C,LDL-C,triglycerides)and obesity-related indicators(waist circumference,waist-to-hip ratio,body fat percentage,and whole-body fat mass)is of great importance for the primary prevention of myocardial infarction.
作者
王绫欢
芦婷婷
张颖杰
王天虎
孙乃媛
陈斯佳
曹丰
Wang Linghuan;Lu Tingting;Zhang Yingjie;Wang Tianhu;Sun Naiyuan;Chen Sijia;Cao Feng(Medicine School of Nankai University,Tianjin 300071,China;Second Medical Center of Chinese People′s Liberation Army General Hospital,National Clinical Research Center for Geriatric Diseases,Beijing 100853,China;Medical School of Chinese People′s Liberation Army General Hospital,Beijing 100853,China)
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2024年第10期1162-1169,共8页
Chinese Journal of Cardiology
基金
国家重点研发计划(2022YFC3602400)
中央保健重点课题(20202D05)
北京自然科学基金项目(L241026)。
关键词
心肌梗死
孟德尔随机化
糖脂代谢紊乱
Myocardial infarction
Mendelian randomization
Glucose and lipid metabolism disorder
作者简介
通信作者:曹丰,Email:fengcao8828@163.com。
