Causality Relationship Between Blood Metabolites and Hypertensive Heart Disease:A Two-sample Bidirectional Mendelian Randomization Study
陈佳永 1唐梅玲 2卢健棋 2庞延 3杨尚冰 1毛美玲 1罗文宽 1张艺博1
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作者信息
1. 530200 南宁,广西中医药大学
2. 530022 南宁,广西中医药大学第一附属医院心血管内科
3. 530022 南宁,广西中医药大学第一附属医院急诊科
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摘要
目的 利用两样本双向孟德尔随机化(Mendelian randomization,MR)分析研究血液代谢产物与高血压性心脏病(hypertensive heart disease,HHD)之间的因果关系.方法 从全基因组关联研究(Genome-Wide Association Study,GW AS)数据库中获取HHD数据.一项包含1400种血液代谢产物的GWAS作为暴露因素,选择与暴露因素显著相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量(instrumental variable,IV).借助 R 软件(V4.3.2)的"TwoSampleMR""gwasglue"等对1400种血液代谢产物与HHD之间的因果关系进行分析.采用MR-Eggeer回归法、加权中位数法(weighted median,WM)、逆方差加权法(inverse-varianceweighted,IVW)等方法,并进行异质性、多效性、敏感度等一系列验证分析.最后进行反向MR分析.结果 通过IVW分析1400种血清代谢产物与HHD之间的因果关系,结果显示,脱氧胆酸-葡萄糖醛酸(OR=0.847,95％CI:0.770～0.931)是保护因素,随着此代谢物的增加,HHD的发病风险反而降低;丁酸/异丁酸(4∶0)(OR=1.316,95％CI:1.134～1.528)是危险因素,随着代谢物的增加,HHD的发病风险越大.结论 丁酸/异丁酸(4∶0)具有促HHD作用,脱氧胆酸-葡萄糖醛酸对HHD具有抑制作用.这可能是未来HHD研究和治疗的新思路、新依据.
Abstract
Objective To evaluate the causal relationship between blood metabolites and hypertensive heart disease(HHD)using two-sample bidirectional Mendelian randomization(MR)analysis.Methods HHD data were obtained from the Genome-wide Associ-ation Study(GWAS)database.A GW AS containing 1400 blood metabolites was used as an exposure factor,and single nucleotide poly-morphism(SNP)significantly associated with exposure factors were selected as instrumental variable(IV).The causal relationship be-tween 1400 blood metabolites and HHD was analyzed by'TwoSampleMR'and'gwasglue'packages of R software(V4.3.2).MR-Eggeer regression method,weighted median(WM)method,and inverse variance weighting(IVW)method and other methods were used.And a series of verification analyses such as heterogeneity,pleiotropic,and sensitivity and so on were performed.Finally,reverse MR a-nalysis was performed.Results IVW analysis of the causal relationship between 1400 blood metabolites and HHD showed that deoxychol-ic acid glucuronic(OR=0.847,95％CI:0.770-0.931)was a protective factor,and the risk of HHD decreased with the increase of this metabolite.Butyric/isobutyric(4∶0)(OR=1.316,95％CI:1.134-1.528)was a risk factor.With the increase of metabolites,the risk of HHD increased.Conclusion Butyric/isobutyric(4∶0)had effect of promoting HHD,and deoxycholic acid glucuronide had effect of inhibiting HHD.This may be a new idea and new basis for the future research and treatment of HHD.
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