Wang Shuang, Yu Zhaoxia, Miller Rachel L, Tang Deliang, Perera Frederica P
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Hum Hered. 2011;71(3):196-208. doi: 10.1159/000328006. Epub 2011 Jul 20.
Genomic imprinting is a form of epigenetic regulation in mammals in which the same allele of a gene is expressed differently depending on the parental origin of the allele. Traditionally, the detection of imprinted genes that affect complex diseases has been focused on linkage designs with pedigrees or case-parent designs with case-parent trios. In the past two decades, the birth cohort design with mother-offspring pairs has been applied to understand better the effect of environmental influences during pregnancy and beginning of life on the growth and development of children. No work has been done on the detection of imprinted genes using birth cohort designs. Moreover, although the importance of imprinting has been well recognized, no study has looked at how environmental exposures modify the effects of imprinted genes. In this study, we show that the proposed imprinting test using the birth cohort design with mother-offspring pairs is an efficient test for testing the interactions between imprinted genes and environmental exposures. Through extensive simulation studies and a real data application, the proposed imprinting test has demonstrated much improved power in detecting gene-environment interactions than that of a test assuming the Mendelian dominant model when the true underlying genetic model is imprinting.
基因组印记是哺乳动物中一种表观遗传调控形式，其中一个基因的相同等位基因根据该等位基因的亲本来源而有不同表达。传统上，检测影响复杂疾病的印记基因主要集中在系谱的连锁设计或病例-双亲三联体的病例-亲本设计上。在过去二十年中，以母婴对为对象的出生队列设计已被用于更好地理解孕期和生命初期的环境影响对儿童生长发育的作用。尚未有研究使用出生队列设计来检测印记基因。此外，尽管印记的重要性已得到充分认识，但尚无研究探讨环境暴露如何改变印记基因的作用。在本研究中，我们表明，所提出的使用母婴对出生队列设计的印记测试是一种用于检验印记基因与环境暴露之间相互作用的有效测试。通过广泛的模拟研究和实际数据应用，当真实的潜在遗传模型为印记时，所提出的印记测试在检测基因-环境相互作用方面比假设孟德尔显性模型的测试具有更高的效能。
