%0 Journal Article %J Science %D 2020 %T The impact of sex on gene expression across human tissues. %A Oliva, Meritxell %A Muñoz-Aguirre, Manuel %A Kim-Hellmuth, Sarah %A Wucher, Valentin %A Gewirtz, Ariel D H %A Cotter, Daniel J %A Parsana, Princy %A Kasela, Silva %A Balliu, Brunilda %A Viñuela, Ana %A Castel, Stephane E %A Mohammadi, Pejman %A Aguet, François %A Zou, Yuxin %A Khramtsova, Ekaterina A %A Skol, Andrew D %A Garrido-Martín, Diego %A Reverter, Ferran %A Brown, Andrew %A Evans, Patrick %A Gamazon, Eric R %A Payne, Anthony %A Bonazzola, Rodrigo %A Barbeira, Alvaro N %A Hamel, Andrew R %A Martinez-Perez, Angel %A Soria, José Manuel %A Pierce, Brandon L %A Stephens, Matthew %A Eskin, Eleazar %A Dermitzakis, Emmanouil T %A Segrè, Ayellet V %A Im, Hae Kyung %A Engelhardt, Barbara E %A Ardlie, Kristin G %A Montgomery, Stephen B %A Battle, Alexis J %A Lappalainen, Tuuli %A Guigo, Roderic %A Stranger, Barbara E %K Chromosomes, Human, X %K Disease %K Epigenesis, Genetic %K Female %K Gene Expression %K Gene Expression Regulation %K Genetic Variation %K Genome-Wide Association Study %K Humans %K Male %K Organ Specificity %K Promoter Regions, Genetic %K Quantitative Trait Loci %K Sex Characteristics %K Sex Factors %X

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.

%B Science %V 369 %8 2020 09 11 %G eng %N 6509 %1 https://www.ncbi.nlm.nih.gov/pubmed/32913072?dopt=Abstract %R 10.1126/science.aba3066