The impact of sex on gene expression across human tissues.

TitleThe impact of sex on gene expression across human tissues.
Publication TypeJournal Article
Year of Publication2020
AuthorsOliva, M, Muñoz-Aguirre, M, Kim-Hellmuth, S, Wucher, V, Gewirtz, ADH, Cotter, DJ, Parsana, P, Kasela, S, Balliu, B, Viñuela, A, Castel, SE, Mohammadi, P, Aguet, F, Zou, Y, Khramtsova, EA, Skol, AD, Garrido-Martín, D, Reverter, F, Brown, A, Evans, P, Gamazon, ER, Payne, A, Bonazzola, R, Barbeira, AN, Hamel, AR, Martinez-Perez, A, Soria, JManuel, Pierce, BL, Stephens, M, Eskin, E, Dermitzakis, ET, Segrè, AV, Im, HKyung, Engelhardt, BE, Ardlie, KG, Montgomery, SB, Battle, AJ, Lappalainen, T, Guigo, R, Stranger, BE
Corporate AuthorsGTEx Consortium
JournalScience
Volume369
Issue6509
Date Published2020 09 11
ISSN1095-9203
KeywordsChromosomes, Human, X, Disease, Epigenesis, Genetic, Female, Gene Expression, Gene Expression Regulation, Genetic Variation, Genome-Wide Association Study, Humans, Male, Organ Specificity, Promoter Regions, Genetic, Quantitative Trait Loci, Sex Characteristics, Sex Factors
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.

DOI10.1126/science.aba3066
Alternate JournalScience
PubMed ID32913072
PubMed Central IDPMC8136152
Grant ListU01 MH104393 / MH / NIMH NIH HHS / United States
R01 MH107666 / MH / NIMH NIH HHS / United States
R01 MH109905 / MH / NIMH NIH HHS / United States
R01 MH106842 / MH / NIMH NIH HHS / United States
U01 HG007598 / HG / NHGRI NIH HHS / United States
K99 HG009916 / HG / NHGRI NIH HHS / United States
R01 HL142028 / HL / NHLBI NIH HHS / United States
R01 HG006855 / HG / NHGRI NIH HHS / United States
R01 MH090951 / MH / NIMH NIH HHS / United States
T32 HG000044 / HG / NHGRI NIH HHS / United States
R01 GM108711 / GM / NIGMS NIH HHS / United States
R01 CA229618 / CA / NCI NIH HHS / United States
UL1 TR000430 / TR / NCATS NIH HHS / United States
R01 HG010480 / HG / NHGRI NIH HHS / United States
R01 DA006227 / DA / NIDA NIH HHS / United States
U41 HG002371 / HG / NHGRI NIH HHS / United States
R01 HG008150 / HG / NHGRI NIH HHS / United States
UM1 HG008901 / HG / NHGRI NIH HHS / United States
U01 HG007593 / HG / NHGRI NIH HHS / United States
R01 GM124486 / GM / NIGMS NIH HHS / United States
R01 MH090936 / MH / NIMH NIH HHS / United States
T32 DK110919 / DK / NIDDK NIH HHS / United States
R01 HG002585 / HG / NHGRI NIH HHS / United States
UL1 TR002550 / TR / NCATS NIH HHS / United States
R01 MH101820 / MH / NIMH NIH HHS / United States
F32 HG009987 / HG / NHGRI NIH HHS / United States
R01 HG010067 / HG / NHGRI NIH HHS / United States
R01 MH090941 / MH / NIMH NIH HHS / United States
R01 GM122924 / GM / NIGMS NIH HHS / United States
U41 HG009494 / HG / NHGRI NIH HHS / United States
R01 MH101822 / MH / NIMH NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
R01 MH090937 / MH / NIMH NIH HHS / United States
HHSN268201000029C / HL / NHLBI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
R01 MH101814 / MH / NIMH NIH HHS / United States
R35 HG010718 / HG / NHGRI NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States