title: Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines.
abstract: The expression level for 15,887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences.
authors.affiliation: Genetic Epidemiology Group, Queensland Institute of Medical Research, Herston, QLD 4029, Australia. allan.mcrae@qimr.edu.au
authors.forename: Allan F
authors.initials: AF
authors.lastname: McRae
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Matigian
authors.forename: Lata
authors.initials: L
authors.lastname: Vadlamudi
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Bryan
authors.initials: B
authors.lastname: Mowry
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Sam F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
mesh_terms: D000328:Adult; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016208:Databases, Factual; D005190:Family; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012727:Sex Characteristics; D014430:Twins, Monozygotic