Influence of sex and genetic variability on expression of X-linked genes in human monocytes

Genomics. 2011 Nov;98(5):320-6. doi: 10.1016/j.ygeno.2011.06.009. Epub 2011 Jul 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Calcium-Binding Proteins / genetics
  • Chromosomes, Human, X / genetics
  • Female
  • Genes, X-Linked*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Monocytes / cytology*
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Sex Factors
  • Transcription, Genetic
  • X Chromosome Inactivation


  • Calcium-Binding Proteins
  • EFHC2 protein, human