Sex differences in the human peripheral blood transcriptome.
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.
Department of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands. ri.jansen@ggzingeest.nl.
Rick
R
Jansen
Sandra
S
Batista
Andrew I
AI
Brooks
Jay A
JA
Tischfield
Gonneke
G
Willemsen
Gerard
G
van Grootheest
Jouke-Jan
JJ
Hottenga
Yuri
Y
Milaneschi
Hamdi
H
Mbarek
Vered
V
Madar
Wouter
W
Peyrot
Jacqueline M
JM
Vink
Cor L
CL
Verweij
Eco J C
EJ
de Geus
Johannes H
JH
Smit
Fred A
FA
Wright
Patrick F
PF
Sullivan
Dorret I
DI
Boomsma
Brenda W J H
BW
Penninx
D000328:Adult; D000367:Age Factors; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D004247:DNA / Q000097:blood* / Q000302:isolation & purification; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D012313:RNA / Q000097:blood* / Q000302:isolation & purification; D012737:Sex Factors; D059467:Transcriptome / Q000187:drug effects*
D003271:Contraceptive Agents, Female; D004967:Estrogens; D012313:RNA; D004247:DNA