title: Methods for detecting interactions between imprinted genes and environmental exposures using birth cohort designs with mother-offspring pairs.
abstract: 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.
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. sw2206@columbia.edu
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Yu
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Miller
authors.forename: Deliang
authors.initials: D
authors.lastname: Tang
authors.forename: Frederica P
authors.initials: FP
authors.lastname: Perera
mesh_terms: D001249:Asthma / Q000235:genetics; D002648:Child; D002877:Chromosomes, Human / Q000235:genetics; D015331:Cohort Studies; D004781:Environmental Exposure; D005220:Fathers; D005260:Female; D005796:Genes / Q000235:genetics*; D056726:Genetic Association Studies; D005819:Genetic Markers; D005821:Genetic Techniques; D018392:Genomic Imprinting / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D009035:Mothers; D036801:Parturition; D011247:Pregnancy; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers