The impact of sex on gene expression across human tissues

TY - JOUR

T1 - The impact of sex on gene expression across human tissues

AU - Oliva, Meritxell

AU - Muñoz-Aguirre, Manuel

AU - Kim-Hellmuth, Sarah

AU - Wucher, Valentin

AU - Gewirtz, Ariel D. H.

AU - Cotter, Daniel J.

AU - Parsana, Princy

AU - Kasela, Silva

AU - Balliu, Brunilda

AU - Viñuela, Ana

AU - Castel, Stephane E.

AU - Mohammadi, Pejman

AU - Aguet, François

AU - Zou, Yuxin

AU - Khramtsova, Ekaterina A.

AU - Skol, Andrew D.

AU - Garrido-Martín, Diego

AU - Reverter, Ferran

AU - Brown, Andrew

AU - Evans, Patrick

AU - Gamazon, Eric R.

AU - Payne, Anthony

AU - Bonazzola, Rodrigo

AU - Barbeira, Alvaro N.

AU - Hamel, Andrew R.

AU - Martinez-Perez, Angel

AU - Soria, José Manuel

AU - GTEx Consortium

AU - Pierce, Brandon L.

AU - Stephens, Matthew

AU - Eskin, Eleazar

AU - Dermitzakis, Emmanouil T.

AU - Segrè, Ayellet V.

AU - Im, Hae Kyung

AU - Engelhardt, Barbara E.

AU - Ardlie, Kristin G.

AU - Montgomery, Stephen B.

AU - Battle, Alexis J.

AU - Lappalainen, Tuuli

AU - Guigó, Roderic

AU - Stranger, Barbara E.

PY - 2020/9/11

Y1 - 2020/9/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85090818936

U2 - 10.1126/science.aba3066

DO - 10.1126/science.aba3066

M3 - Article

C2 - 32913072

AN - SCOPUS:85090818936

SN - 0036-8075

VL - 369

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6509

M1 - eaba3066

ER -