孟德尔随机化分析原理解析.ppt

MendelianRandomisationstudy MendelianRandomisationstudy SNPs 25OHD AsthmaChildhoodasthmaAtopicdermatitisIgE Confounders BMI Smoking Pleiotropy eosinophils StandardizedplaninMendelianrandomisationstudy ExtractinterestingSNPs Extractdataofcasesandcontrols Two sampleMR PotentialproblemsandlimitationsofMendelianrandomisationstudy ValidateSNPs ExtractinterestingSNPs Pvalue 5 10 81 SUNLIGHTConsortium CanadianMulticentreOsteoporosisStudy CaMos 2 FromthelargestGWA UKBiobank 3 FromtheGIANT GeneticInvestigationofAnthropometricTraits consortiumeg BMI Height Extractdataofcasesandcontrols UKBiobankAsthma hildrenAsthma GABRIELconsortium Atopicdermatitis EAGLEEczemaConsortium IgElevels GABRIELconsortium EarlyGeneticsandLifecourseEpidemiology EAGLE EczemaConsortium HavethedetailinformationofinterestedSNPsincasesandcontrols Two sampleMR Eg Therelationshipbetweengeneticvariantsand25OHDwasascertainedfromonestudy andtherelationshipbetweenthesamegeneticvariantsandAsthma Childhoodasthma Atopicdermatitis IgEwasascertainedfromasecondstudy Waldratios IV ZY ZX ZXSNP与暴露或中间表现的相关系数 ZYSNP与目标结局的相关系数 ValidateSNPs 1 F statistic 验证每个SNP是否为虚弱工具变量F 10 2回归系数的平方F 2 n 2 1 2 2 LD分析 2andD dumpingSNPs indexSNP3 populationstratification分析4 Pleiotropy分析 基因图谱 遗传距离 染色体上位置以及蛋白通道 SNPsexposuresoutcome非研究暴露 5 敏感性分析 依次剔除功能相似 在同一基因上或附近的SNPs 验证MR三个假设 线性回归 Logistic回归 meta分析 分析SNPs与中间表型的相关性 分析SNPs与已知混杂因素的相关性 目标SNPs对结局的作用必须只能通过已知的研究表型 PotentialproblemsandlimitationsofMendelianrandomisationstudy Non linearassociationsWeakinstrumentsLinkagedisequilibriumPopula