Sex differences in the human peripheral blood transcriptome

BMC Genomics. 2014 Jan 17;15:33. doi: 10.1186/1471-2164-15-33.


Background: Genomes of men and women differ in only a limited number of genes located on the sex chromosomes, whereas the transcriptome is far more sex-specific. Identification of sex-biased gene expression will contribute to understanding the molecular basis of sex-differences in complex traits and common diseases.

Results: Sex differences in the human peripheral blood transcriptome were characterized using microarrays in 5,241 subjects, accounting for menopause status and hormonal contraceptive use. Sex-specific expression was observed for 582 autosomal genes, of which 57.7% was upregulated in women (female-biased genes). Female-biased genes were enriched for several immune system GO categories, genes linked to rheumatoid arthritis (16%) and genes regulated by estrogen (18%). Male-biased genes were enriched for genes linked to renal cancer (9%). Sex-differences in gene expression were smaller in postmenopausal women, larger in women using hormonal contraceptives and not caused by sex-specific eQTLs, confirming the role of estrogen in regulating sex-biased genes.

Conclusions: This study indicates that sex-bias in gene expression is extensive and may underlie sex-differences in the prevalence of common diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Chromosomes, Human, X
  • Chromosomes, Human, Y
  • Contraceptive Agents, Female / pharmacology
  • DNA / blood*
  • DNA / isolation & purification
  • Estrogens / metabolism
  • Female
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Postmenopause
  • RNA / blood*
  • RNA / isolation & purification
  • Sex Factors
  • Transcriptome / drug effects*


  • Contraceptive Agents, Female
  • Estrogens
  • RNA
  • DNA