The impact of sex on gene expression across human tissues

Oliva, Meritxell; Munoz-Aguirre, Manuel; Kim-Hellmuth, Sarah; Wucher, Valentin; Gewirtz, Ariel D. H.; Cotter, Daniel J.; Parsana, Princy; Kasela, Silva; Balliu, Brunilda; Vinuela, Ana; Castel, Stephane E.; Mohammadi, Pejman; Aguet, Francois; Zou, Yuxin; Khramtsova, Ekaterina A.; Skol, Andrew D.; Garrido-Martin, Diego; Reverter, Ferran; Brown, Andrew; Evans, Patrick; Gamazon, Eric R.; Payne, Anthony; Bonazzola, Rodrigo; Barbeira, Alvaro N.; Hamel, Andrew R.; Martinez-Perez, Angel; Soria, Jose Manuel; Pierce, Brandon L.; Stephens, Matthew; Eskin, Eleazar; Dermitzakis, Emmanouil T.; Segr, Ayellet V.; Im, Hae Kyung; Engelhardt, Barbara E.; Ardlie, Kristin G.; Montgomery, Stephen B.; Battle, Alexis J.; Lappalainen, Tuuli; Guigo, Roderic und Stranger, Barbara E. (2020): The impact of sex on gene expression across human tissues. In: Science, Bd. 369, Nr. 6509, eaba3066

Abstract

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0036-8075
• Sprache: Englisch