Sex-dependent gene co-expression in the human body

Abstract Many pathophysiological mechanisms in human health and disease are dependent on sex. Systems biology approaches are successfully used to decipher human disease etiology, yet the effect of sex on gene network biology is mostly unknown. To address this, we used RNA-sequencing data of over 700...

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Autores principales:	Robin J. G. Hartman, Michal Mokry, Gerard Pasterkamp, Hester M. den Ruijter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c443e7d500cc4b688f8efefdf10eda2b
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spelling	oai:doaj.org-article:c443e7d500cc4b688f8efefdf10eda2b2021-12-02T18:14:39ZSex-dependent gene co-expression in the human body10.1038/s41598-021-98059-92045-2322https://doaj.org/article/c443e7d500cc4b688f8efefdf10eda2b2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98059-9https://doaj.org/toc/2045-2322Abstract Many pathophysiological mechanisms in human health and disease are dependent on sex. Systems biology approaches are successfully used to decipher human disease etiology, yet the effect of sex on gene network biology is mostly unknown. To address this, we used RNA-sequencing data of over 700 individuals spanning 24 tissues from the Genotype-Tissue Expression project to generate a whole-body gene co-expression map and quantified the sex differences per tissue. We found that of the 13,787 genes analyzed in 24 tissues, 29.5% of the gene co-expression is influenced by sex. For example, skeletal muscle was predominantly enriched with genes co-expressed stronger in males, whereas thyroid primarily contained genes co-expressed stronger in females. This was accompanied by consistent sex differences in pathway enrichment, including hypoxia, epithelial-to-mesenchymal transition, and inflammation over the human body. Furthermore, multi-organ analyses revealed consistent sex-dependent gene co-expression over numerous tissues which was accompanied by enrichment of transcription factor binding motifs in the promoters of these genes. Finally, we show that many sex-biased genes are associated with sex-biased diseases, such as autoimmunity and cancer, and more often the target of FDA-approved drugs than non-sexbiased genes. Our study suggests that sex affects biological gene networks by differences in gene co-expression and that attention to the effect of sex on biological responses to medical drugs is warranted.Robin J. G. HartmanMichal MokryGerard PasterkampHester M. den RuijterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robin J. G. Hartman Michal Mokry Gerard Pasterkamp Hester M. den Ruijter Sex-dependent gene co-expression in the human body
description	Abstract Many pathophysiological mechanisms in human health and disease are dependent on sex. Systems biology approaches are successfully used to decipher human disease etiology, yet the effect of sex on gene network biology is mostly unknown. To address this, we used RNA-sequencing data of over 700 individuals spanning 24 tissues from the Genotype-Tissue Expression project to generate a whole-body gene co-expression map and quantified the sex differences per tissue. We found that of the 13,787 genes analyzed in 24 tissues, 29.5% of the gene co-expression is influenced by sex. For example, skeletal muscle was predominantly enriched with genes co-expressed stronger in males, whereas thyroid primarily contained genes co-expressed stronger in females. This was accompanied by consistent sex differences in pathway enrichment, including hypoxia, epithelial-to-mesenchymal transition, and inflammation over the human body. Furthermore, multi-organ analyses revealed consistent sex-dependent gene co-expression over numerous tissues which was accompanied by enrichment of transcription factor binding motifs in the promoters of these genes. Finally, we show that many sex-biased genes are associated with sex-biased diseases, such as autoimmunity and cancer, and more often the target of FDA-approved drugs than non-sexbiased genes. Our study suggests that sex affects biological gene networks by differences in gene co-expression and that attention to the effect of sex on biological responses to medical drugs is warranted.
format	article
author	Robin J. G. Hartman Michal Mokry Gerard Pasterkamp Hester M. den Ruijter
author_facet	Robin J. G. Hartman Michal Mokry Gerard Pasterkamp Hester M. den Ruijter
author_sort	Robin J. G. Hartman
title	Sex-dependent gene co-expression in the human body
title_short	Sex-dependent gene co-expression in the human body
title_full	Sex-dependent gene co-expression in the human body
title_fullStr	Sex-dependent gene co-expression in the human body
title_full_unstemmed	Sex-dependent gene co-expression in the human body
title_sort	sex-dependent gene co-expression in the human body
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c443e7d500cc4b688f8efefdf10eda2b
work_keys_str_mv	AT robinjghartman sexdependentgenecoexpressioninthehumanbody AT michalmokry sexdependentgenecoexpressioninthehumanbody AT gerardpasterkamp sexdependentgenecoexpressioninthehumanbody AT hestermdenruijter sexdependentgenecoexpressioninthehumanbody
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Sex-dependent gene co-expression in the human body

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