title: Epistatic and environmental control of genome-wide gene expression.
abstract: All etiological studies of complex human traits focus on analyzing the causes of variation. Given this complexity, there is a premium on studying those processes that mediate between gene products and cellular or organismal phenotypes. Studies of levels of gene expression could offer insight into these processes and are likely to be especially useful to the extent that the major sources of their variation are known in normal tissues. The classical study of monozygotic (MZ) and dizygotic (DZ) twins was employed to partition the genetic and environmental influences in gene expression for over 6500 human genes measured using microarrays from lymphoblastoid cell lines. Our results indicate that mean expression levels are correlated about .3 in monozygotic (MZ) and .0 in dizygotic (DZ) twins suggesting an overall epistatic regulation of gene expression. Furthermore, the functions of several of the genes whose expression was most affected by environmental effects, after correction for measurement error, were consistent with their known role in mediating sensitivity to environmental influences.
authors.affiliation: Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298-0003, USA. tpyork@vcu.edu
authors.forename: Timothy P
authors.initials: TP
authors.lastname: York
authors.forename: Michael F
authors.initials: MF
authors.lastname: Miles
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Colleen
authors.initials: C
authors.lastname: Jackson-Cook
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Bowman
authors.forename: Lindon J
authors.initials: LJ
authors.lastname: Eaves
mesh_terms: D000293:Adolescent; D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D004777:Environment; D004843:Epistasis, Genetic; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*