TY - JOUR
T1 - Influence of sex and genetic variability on expression of X-linked genes in human monocytes
AU - Castagné, Raphaële
AU - Zeller, Tanja
AU - Rotival, Maxime
AU - Szymczak, Silke
AU - Truong, Vinh
AU - Schillert, Arne
AU - Trégouët, David Alexandre
AU - Münzel, Thomas
AU - Ziegler, Andreas
AU - Cambien, François
AU - Blankenberg, Stefan
AU - Tiret, Laurence
N1 - Funding Information:
The Gutenberg Heart Study is funded through the government of Rheinland-Pfalz (“Stiftung Rheinland Pfalz für Innovation ”, contract AZ 961-386261/733 ), the research programs “Wissen schafft Zukunft” and “Schwerpunkt Vaskuläre Prävention” of the Johannes Gutenberg-University of Mainz and its contract with Boehringer Ingelheim and PHILIPS Medical Systems including an unrestricted grant for the Gutenberg Heart Study. The present study was supported by the National Genome Network “NGFNplus ” (contract A3 01GS0833 and 01GS0831 ) and by a joint funding from the Federal Ministry of Education and Research , Germany (contract BMBF 01KU0908A ) and from the Agence Nationale de la Recherche , France (contract ANR 09 GENO 106 01 ) for the project CARDomics. Statistical analysis benefited from the C2BIG platform supported by the Fondation pour la Recherche Médicale and the Région Ile-de-France.
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80055065043&partnerID=8YFLogxK
U2 - 10.1016/j.ygeno.2011.06.009
DO - 10.1016/j.ygeno.2011.06.009
M3 - Journal articles
C2 - 21763416
AN - SCOPUS:80055065043
SN - 0888-7543
VL - 98
SP - 320
EP - 326
JO - Genomics
JF - Genomics
IS - 5
ER -
