孟德尔随机化分析原理解析

操作演示
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Eczema Consortium
@ Have the detail information of interested SNPs in cases and
controls
Two-sample MR
Eg. The relationship between genetic variants and 25OHD was
Potential problems and limitations of Mendelian randomisation study
1. Non-linear associations 2. Weak instruments 3. Linkage disequilibrium 4. Population stratification 5. undertake subgroup analyses 6. Don’t to gain mechanistic insights
Extract interesting SNPs
P value < 5 × 10−8
1.SUNLIGHT Consortium, Canadian Multicentre Osteoporosis Study
(CaMos)
2.From the largest GWA(UK Biobank)
3.From the GIANT (Genetic Investigation of Anthropometric Traits) consortium eg . BMI, Height
ascertained from one study, and the relationship between the same genetic variants and Asthma, Childhood asthma, Atopic dermatitis, IgE was ascertained from a second study.
Extract interesting SNPs Extract data of cases and
controls Two-sample MR
Validate SNPs
Potential problems and limitations of Mendelian randomisation study
Extract data of cases and controls
UK Biobank
Asthma , hildren Asthma (GABRIEL consortium ) Atopic dermatitis (EAGLE Eczema Consortium) IgE levels (GABRIEL consortium) Early Genetics and Lifecourse Epidemiology (EAGLE)
孟德尔随机化分析原理解析
Mendelian Randomisation study
Pleiotropy (eosinophils)
SNPs
25Fra Baidu bibliotekHD
Asthma Childhood asthma Atopic dermatitis IgE
Confounders (BMI,Smoking)
Standardized plan in Mendelian randomisation study
Wald ratios (βIV)= βZY/βZX βZX SNP与暴露或中间表现的相关系数 βZY SNP与目标结局的相关系数
Validate SNPs
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）
a. 分析SNPs与中间表型的相关性（+） b. 分析SNPs与已知混杂因素的相关性（-） c. 目标SNPs对结局的作用必须只能通过已知的研究表型