Abstract

Sex differences in endothelial cell (EC) biology may reflect intrinsic differences driven by chromosomes or sex steroid exposure and gender differences accumulated over life. We analysed EC gene expression data from boy–girl twins at birth and in non-twin adults to detect sex differences at different stages of life, and show that 14–25% of the EC transcriptome is sex-biased. By combining data from both stages of life, we identified sex differences that are present at birth and maintained throughout life, and those that are acquired over life. Promisingly, we found that genes that present with an acquired sex difference in ECs are more likely to be targets of sex steroids. Annotating both gene sets with data from multiple genome-wide association studies (GWAS) revealed that genes with an intrinsic sex difference in ECs are enriched for coronary artery disease GWAS hits. This study underscores the need for treating sex as a biological variable.

Details

Title
Intrinsic transcriptomic sex differences in human endothelial cells at birth and in adults are associated with coronary artery disease targets
Author
Hartman, Robin J, G 1 ; Kapteijn, Daniek M, C 1 ; Haitjema Saskia 2 ; Bekker, Mireille N 3 ; Mokry Michal 4 ; Pasterkamp Gerard 2 ; Civelek Mete 5 ; den Ruijter Hester M 6 

 University Medical Center Utrecht, Laboratory of Experimental Cardiology, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352) 
 University Medical Center Utrecht, Central Diagnostics Laboratory, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352) 
 University Medical Center Utrecht, Department of Obstetrics and Gynecology, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352) 
 University Medical Center Utrecht, Laboratory of Experimental Cardiology, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352); University Medical Center Utrecht, Central Diagnostics Laboratory, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352) 
 University of Virginia, Center for Public Health Genomics, Department of Biomedical Engineering, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
 University Medical Center Utrecht, Laboratory of Experimental Cardiology, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352); University Medical Center Utrecht, Division of Heart and Lungs, Department of Experimental Cardiology, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2426371645
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.