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BAYESIAN GROUP LASSO FOR NONPARAMETRIC VARYING-COEFFICIENT MODELS WITH APPLICATION TO FUNCTIONAL GENOME-WIDE ASSOCIATION STUDIES

机译:非参数变系数模型的贝叶斯族LASSO及其在功能基因组关联研究中的应用

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摘要

Although genome-wide association studies (GWAS) have proven powerful for comprehending the genetic architecture of complex traits, they are challenged by a high dimension of single-nucleotide polymorphisms (SNPs) as predictors, the presence of complex environmental factors, and longitudinal or functional natures of many complex traits or diseases. To address these challenges, we propose a high-dimensional varying-coefficient model for incorporating functional aspects of phenotypic traits into GWAS to formulate a so-called functional GWAS or fGWAS. Bayesian group lasso and the associated MCMC algorithms are developed to identify significant SNPs and estimate how they affect longitudinal traits through time-varying genetic actions. The model is generalized to analyze the genetic control of complex traits using subject-specific sparse longitudinal data. The statistical properties of the new model are investigated through simulation studies. We use the new model to analyze a real GWAS data set from the Framingham Heart Study, leading to the identification of several significant SNPs associated with age-specific changes of body mass index. The fGWAS model, equipped with Bayesian group lassso, will provide a useful tool for genetic and developmental analysis of complex traits or diseases.
机译:尽管全基因组关联研究(GWAS)已证明对理解复杂性状的遗传结构具有强大的作用,但它们仍面临着高维度的单核苷酸多态性(SNP)作为预测因子,复杂的环境因素以及纵向或功能性的挑战。许多复杂特征或疾病的性质。为了解决这些挑战,我们提出了一个高维变化系数模型,用于将表型性状的功能方面纳入GWAS,以制定所谓的功能GWAS或fGWAS。贝叶斯组套索和相关的MCMC算法被开发出来,以识别重要的SNP,并估计它们如何通过时变的遗传作用影响纵向性状。该模型被概括为使用特定于对象的稀疏纵向数据来分析复杂性状的遗传控制。通过仿真研究来研究新模型的统计特性。我们使用新模型来分析来自Framingham心脏研究的真实GWAS数据集,从而识别出与年龄指数相关的几个重要SNP。装有贝叶斯族lassso的fGWAS模型将为复杂性状或疾病的遗传和发育分析提供有用的工具。

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