title: Modulation of gene expression by genetic and environmental heterogeneity in timing of a developmental milestone.
abstract: The expression of many important behavioral outcomes is contingent on passing a developmental milestone, such as puberty, or exposure to an age-dependent risk factor, such as alcohol or drugs. Current models for genetic effects on development have not provided explicit theoretical insight about possible patterns of epistasis and genotype x environment interaction generated by genetic and environmental heterogeneity in the timing of developmental milestones that influence gene expression. We explore theoretically the effects of individual differences in the timing of a developmental milestone on the expression of genetic differences in outcome. The consequences of additive genetic variation and shared environmental variation on timing are examined. Additive genetic effects on timing generate transient epistatic effects on outcome because they modulate the expression of otherwise additive genetic differences in outcome. Epistatic effects will be greatest at ages when there is the most heterogeneity in developmental maturity. Epistasis will gradually disappear as proportionately more individuals mature. Similarly, shared environmental effects on the timing of a milestone will generate transient genotype x shared environment interaction appearing as shared environmental effects on outcome that are greatest when there is the most heterogeneity in developmental maturity. The impact of these effects on age patterns in twin correlations is examined and their relevance to current data on developmental change discussed briefly.
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0003, USA.
authors.forename: Lindon J
authors.initials: LJ
authors.lastname: Eaves
authors.forename: Judy L
authors.initials: JL
authors.lastname: Silberg
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D004777:Environment; D004843:Epistasis, Genetic; D015870:Gene Expression; D018740:Genetic Heterogeneity; D014644:Genetic Variation; D006803:Human Development; D006801:Humans; D008957:Models, Genetic; D012307:Risk Factors; D013223:Statistics as Topic; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic