基于GWAS数据分析肠道菌群与脑出血的关系

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data

目的:自发性脑出血(intracerebral hemorrhage,ICH)在脑卒中各亚型中病死率、致残率最高,既往研究表明肠道菌群(gut microbiome,GM)与ICH的危险因素和病理基础密切相关。本研究旨在探索两者的因果关联及GM对ICH发病的潜在作用机制。方法:从微生物基因组联盟及国际脑卒中协会获取有关GM和ICH的全基因组关联分析(genome wide association study,GWAS)数据,对GWAS数据使用孟德尔随机化(Mendelian randomization,MR)分析探讨GM与ICH的因果关联,运用条件错误发现率(conditional false discovery rate,cFDR)法识别两者的多效性易感遗传变异。结果:MR分析结果显示:Pasteurellales目、Pasteurellaceae科、Haemophilus属的GM与ICH有负向因果效应;Verrucomicrobiae纲、Verrucomicrobiales目、Verrucomicrobiaceae科、Akkermansia属、Holdemanella属和LachnospiraceaeUCG010属的GM与ICH有正向因果效应。通过cFDR法识别出GM与ICH的3个多效性遗传位点,分别为rs331083、rs4315115和rs12553325。结论:GM与ICH发病存在因果关联和多效性易感遗传变异。

Objective:Intracerebral hemorrhage(ICH)has the highest mortality and disability rates among various subtypes of stroke.Previous studies have shown that the gut microbiome(GM)is closely related to the risk factors and pathological basis of ICH.This study aims to explore the causal effect of GM on ICH and the potential mechanisms.Methods:Genome wide association study(GWAS)data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium.Based on the GWAS data,we first performed Mendelian randomization(MR)analysis to evaluate the causal association between GM and ICH.Then,a conditional false discovery rate(cFDR)method was conducted to identify the pleiotropic variants.Results:MR analysis showed that Pasteurellales,Pasteurellaceae,and Haemophilus were negatively correlated with the risk of ICH,while Verrucomicrobiae,Verrucomicrobiales,Verrucomicrobiaceae,Akkermansia,Holdemanella,and LachnospiraceaeUCG010 were positively correlated with ICH.By applying the cFDR method,3 pleiotropic loci(rs331083,rs4315115,and rs12553325)were found to be associated with both GM and ICH.Conclusion:There is a causal association and pleiotropic variants between GM and ICH.