title: Influence of sex and genetic variability on expression of X-linked genes in human monocytes.
abstract: In humans, the fraction of X-linked genes with higher expression in females has been estimated to be 5% from microarray studies, a proportion lower than the 25% of genes thought to escape X inactivation. We analyzed 715 X-linked transcripts in circulating monocytes from 1,467 subjects and found an excess of female-biased transcripts on the X compared to autosomes (9.4% vs 5.5%, p<2×10(-5)). Among the genes not previously known to escape inactivation, the most significant one was EFHC2 whose 20% of variability was explained by sex. We also investigated cis expression quantitative trait loci (eQTLs) by analyzing 15,703 X-linked SNPs. The frequency and magnitude of X-linked cis eQTLs were quite similar in males and females. Few genes exhibited a stronger genetic effect in females than in males (ARSD, DCX, POLA1 and ITM2A). These genes would deserve further investigation since they may contribute to sex pathophysiological differences.
authors.affiliation: Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, Paris, France. raphaele.castagne@upmc.fr
authors.forename: Raphaële
authors.initials: R
authors.lastname: Castagné
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.forename: Maxime
authors.initials: M
authors.lastname: Rotival
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.forename: Vinh
authors.initials: V
authors.lastname: Truong
authors.forename: Arne
authors.initials: A
authors.lastname: Schillert
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
mesh_terms: D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D050172:Genes, X-Linked; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012737:Sex Factors; D014158:Transcription, Genetic; D049951:X Chromosome Inactivation
chemical_list: D002135:Calcium-Binding Proteins; C521068:EFHC2 protein, human