Extensions of Mendelian Randomization Methodology for Combined Genomic and Methylomic Analysis

项目摘要 该项目旨在开发和应用新的统计方法来解决关键问题， 药物使用、滥用和依赖中的因果关系问题。的 开发将侧重于扩展孟德尔随机化方法， 测试其关键假设的新数据类型。这些发展包括： 估计和控制非随机交配引起的偏倚;数据分析 来自无关但基因分型的个体;扩展到纵向数据; 多变量网络模型;以及多组分析，以测试性别、年龄和 其他群体差异。这些新方法将应用于独特的纵向 吸烟者和非吸烟者的表型、基因型和甲基化数据， 荷兰双胞胎登记处和英国生物银行的数据。的精确鉴别 因果途径将使基于证据的预防和治疗方法， 设计和实施。

Project Summary This project aims to develop and apply novel statistical approaches to address key causal questions in the of substance use, abuse and dependence. The development will focus on extending Mendelian Randomization methodology to new data types that test its key assumptions. These developments include: estimating and controlling for biases due to non- random mating; analyses of data from unrelated but genotyped individuals; extension to longitudinal data; multivariate network models; and multiple-group analyses to test for sex, age and other group differences. These new methods will be applied to unique longitudinal phenotype, genotype and methylation data on smokers and non- smokers from the Netherlands Twin Register, and data from the UK biobank. Precise identification of causal pathways will enable evidence- based prevention and treatment methods to be devised and implemented.