title: A statistical design for testing transgenerational genomic imprinting in natural human populations.
abstract: Genomic imprinting is a phenomenon in which the same allele is expressed differently, depending on its parental origin. Such a phenomenon, also called the parent-of-origin effect, has been recognized to play a pivotal role in embryological development and pathogenesis in many species. Here we propose a statistical design for detecting imprinted loci that control quantitative traits based on a random set of three-generation families from a natural population in humans. This design provides a pathway for characterizing the effects of imprinted genes on a complex trait or disease at different generations and testing transgenerational changes of imprinted effects. The design is integrated with population and cytogenetic principles of gene segregation and transmission from a previous generation to next. The implementation of the EM algorithm within the design framework leads to the estimation of genetic parameters that define imprinted effects. A simulation study is used to investigate the statistical properties of the model and validate its utilization. This new design, coupled with increasingly used genome-wide association studies, should have an immediate implication for studying the genetic architecture of complex traits in humans.
authors.affiliation: Center for Computational Biology, Beijing Forestry University, Beijing, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Guo
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Myron N
authors.initials: MN
authors.lastname: Chang
authors.forename: Duanping
authors.initials: D
authors.lastname: Liao
authors.forename: Rongling
authors.initials: R
authors.lastname: Wu
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D015340:Epidemiologic Research Design; D005191:Family Characteristics; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data; D018392:Genomic Imprinting / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008297:Male; D015233:Models, Statistical