Xu Lizhen, Craiu Radu V, Derkach Andriy, Paterson Andrew D, Sun Lei
Department of Statistical Sciences, University of Toronto, Toronto, Ontario M5S 3G3, Canada.
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto M5G 1X8, Canada ; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Ontario M5S 3G3, Canada.
BMC Proc. 2014 Jun 17;8(Suppl 1 Genetic Analysis Workshop 18Vanessa Olmo):S77. doi: 10.1186/1753-6561-8-S1-S77. eCollection 2014.
Pleiotropy, which occurs when a single genetic factor influences multiple phenotypes, is present in many genetic studies of complex human traits. Longitudinal family data, such as the Genetic Analysis Workshop 18 data, combine the features of longitudinal studies in individuals and cross-sectional studies in families, thus providing richer information about the genetic and environmental factors associated with the trait of interest. We recently proposed a Bayesian latent variable methodology for the study of pleiotropy, in the presence of longitudinal and family correlation. The purpose of this work is to evaluate the Bayesian latent variable method in a real data setting using the Genetic Analysis Workshop 18 blood pressure phenotypes and sequenced genotype data. To detect single-nucleotide polymorphisms with pleiotropic effect on both diastolic and systolic blood pressure, we focused on a set of 6 single-nucleotide polymorphisms from chromosome 3 that was reported in the literature to be significantly associated with either diastolic blood pressure or the binary hypertension trait. Our analysis suggests that both diastolic blood pressure and systolic blood pressure are associated with the latent hypertension severity variable, but the analysis did not find any of the 6 single-nucleotide polymorphisms to have statistically significant pleiotropic effect on both diastolic blood pressure and systolic blood pressure.
多效性是指单个基因因素影响多种表型的情况,在许多复杂人类性状的基因研究中都存在。纵向家庭数据,如遗传分析研讨会18的数据,结合了个体纵向研究和家庭横断面研究的特点,从而提供了关于与感兴趣性状相关的遗传和环境因素的更丰富信息。我们最近提出了一种贝叶斯潜在变量方法,用于在存在纵向和家庭相关性的情况下研究多效性。这项工作的目的是使用遗传分析研讨会18的血压表型和测序基因型数据,在实际数据环境中评估贝叶斯潜在变量方法。为了检测对舒张压和收缩压都有多效性影响的单核苷酸多态性,我们聚焦于文献报道的与舒张压或二元高血压性状显著相关的来自3号染色体的一组6个单核苷酸多态性。我们的分析表明,舒张压和收缩压都与潜在的高血压严重程度变量相关,但分析未发现这6个单核苷酸多态性中的任何一个对舒张压和收缩压都有统计学上显著的多效性影响。