Zhang Fangyuan, Lin Shili
Department of Statistics, The Ohio State University, 1958 Neil Avenue Columbus, OH, 43210, USA.
BMC Proc. 2014 Jun 17;8(Suppl 1):S52. doi: 10.1186/1753-6561-8-S1-S52. eCollection 2014.
Imprinting effects can lead to parent-of-origin patterns in many complex human diseases. For hypertension, previous studies revealed the possible involvement of imprinted genes. Genetic Analysis Workshop 18 real data, with hypertensive phenotype and genotype of more than 1000 individuals from 20 pedigrees, provided us an opportunity to further substantiate such findings. To test for imprinting effects, we developed a pedigree-parental-asymmetry test taking both affected and unaffected offspring into consideration (PPATu). We carried out a simulation study based on the Genetic Analysis Workshop 18 pedigrees to show that PPATu has well-controlled type I error and is indeed more powerful than the pedigree-parental-asymmetry test (PPAT), an existing method that does not utilize information from unaffected offspring. We then applied PPATu to Genetic Analysis Workshop 18 genome-wide association study data from 20 pedigrees. We identified a number of single-nucleotide polymorphisms showing significant imprinting effects that are within genomic regions that have been previously implicated to be associated with hypertension.
印记效应可导致许多复杂人类疾病中出现源自亲本的模式。对于高血压，先前的研究揭示了印记基因可能参与其中。遗传分析研讨会18的真实数据包含来自20个家系的1000多名个体的高血压表型和基因型，为我们进一步证实这些发现提供了机会。为了检验印记效应，我们开发了一种兼顾患病和未患病后代的家系亲本不对称检验方法（PPATu）。我们基于遗传分析研讨会18的家系进行了模拟研究，结果表明PPATu具有良好控制的I型错误率，并且实际上比家系亲本不对称检验方法（PPAT）更具效力，PPAT是一种现有方法，未利用未患病后代的信息。然后，我们将PPATu应用于遗传分析研讨会18中来自20个家系的全基因组关联研究数据。我们识别出了一些单核苷酸多态性，这些多态性在先前已被认为与高血压相关的基因组区域内表现出显著的印记效应。
