The impact of sex on gene expression across human tissues.
Meritxell OlivaManuel Muñoz-AguirreSarah Kim-HellmuthValentin WucherAriel D H GewirtzDaniel J CotterPrincy ParsanaSilva KaselaBrunilda BalliuAna ViñuelaStephane E CastelPejman MohammadiFrançois AguetYuxin ZouEkaterina A KhramtsovaAndrew D SkolDiego Garrido-MartínFerran ReverterAndrew Anand BrownPatrick EvansEric R GamazonAnthony PayneRodrigo BonazzolaAlvaro N BarbeiraAndrew R HamelAngel Martinez-PerezJosé Manuel Sorianull nullBrandon L PierceMatthew StephensEleazar EskinEmmanouil T DermitzakisAyellet V SegrèHae Kyung ImBarbara Elizabeth EngelhardtKristin G ArdlieStephen B MontgomeryAlexis J BattleTuuli LappalainenRoderic GuigoBarbara E StrangerPublished in: Science (New York, N.Y.) (2020)
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.