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

Raphaële Castagné; Tanja Zeller; Maxime Rotival; Silke Szymczak; Vinh Truong; Arne Schillert; David Alexandre Trégouët; Thomas Münzel; Andreas Ziegler; François Cambien; Stefan Blankenberg; Laurence Tiret

doi:10.1016/j.ygeno.2011.06.009

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

Raphaële Castagné^*, Tanja Zeller, Maxime Rotival, Silke Szymczak, Vinh Truong, Arne Schillert, David Alexandre Trégouët, Thomas Münzel, Andreas Ziegler, François Cambien, Stefan Blankenberg, Laurence Tiret

^*Corresponding author for this work

Institute of Medical Biometry and Statistic

22 Citations (Scopus)

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.

Original language	English
Journal	Genomics
Volume	98
Issue number	5
Pages (from-to)	320-326
Number of pages	7
ISSN	0888-7543
DOIs	https://doi.org/10.1016/j.ygeno.2011.06.009
Publication status	Published - 11.2011

Funding

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.

Research Areas and Centers

Research Area: Medical Genetics

DFG Research Classification Scheme

2.22-01 Epidemiology, Medical Biometry/Statistics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ygeno.2011.06.009

Cite this

@article{e6027672348142d789d133605b61a08c,

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.",

author = "Rapha{\"e}le Castagn{\'e} and Tanja Zeller and Maxime Rotival and Silke Szymczak and Vinh Truong and Arne Schillert and Tr{\'e}gou{\"e}t, \{David Alexandre\} and Thomas M{\"u}nzel and Andreas Ziegler and Fran{\c c}ois Cambien and Stefan Blankenberg and Laurence Tiret",

note = "Funding Information: The Gutenberg Heart Study is funded through the government of Rheinland-Pfalz (“Stiftung Rheinland Pfalz f{\"u}r Innovation ”, contract AZ 961-386261/733 ), the research programs “Wissen schafft Zukunft” and “Schwerpunkt Vaskul{\"a}re Pr{\"a}vention” 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 M{\'e}dicale and the R{\'e}gion Ile-de-France. ",

year = "2011",

month = nov,

doi = "10.1016/j.ygeno.2011.06.009",

language = "English",

volume = "98",

pages = "320--326",

journal = "Genomics",

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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.

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DO - 10.1016/j.ygeno.2011.06.009

M3 - Journal articles

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AN - SCOPUS:80055065043

SN - 0888-7543

VL - 98

SP - 320

EP - 326

JO - Genomics

JF - Genomics

IS - 5

ER -

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

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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