Journal
SCIENCE
Volume 369, Issue 6509, Pages 1331-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aba3066
Keywords
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Categories
Funding
- Common Fund of the Office of the Director, U.S. National Institutes of Health
- NCI
- NHGRI
- NHLBI
- NIDA
- NIMH
- NIA
- NIAID
- NINDS through NIH (NCI) [HHSN261200800001E]
- NINDS through NIH (NDRI) [10XS170]
- NINDS through NIH (Roswell Park Cancer Institute) [10XS171]
- NINDS through NIH (Science Care Inc.) [10X172]
- NINDS through NIH (IDOX) [12ST1039]
- NINDS through NIH (Van Andel Institute) [10ST1035]
- NINDS through NIH (Broad Institute) [HHSN268201000029C]
- NINDS through NIH [5U41HG009494]
- NIH (Univ. of Miami Brain Bank) [R01 DA006227-17]
- University of Miami [DA006227]
- Univ. of Geneva [R01 MH090941]
- Univ. of Chicago [R01 MH090951, R01 MH090937]
- Univ. of North Carolina-Chapel Hill [R01 MH090936]
- Gordon and Betty Moore Foundation GBMF [4559, 1K99HG009916-01, R01HG006855, BIO2015-70777-P]
- Ministerio de Economia y Competitividad
- FEDER funds
- la Caixa Foundation [100010434, LCF/BQ/SO15/52260001]
- NIH CTSA [UL1TR002550-01]
- Marie-Sklodowska Curie fellowship H2020 [706636, R35HG010718, FPU15/03635]
- Ministerio de Educacion, Cultura y Deporte [R01MH109905, 1R01HG010480]
- Searle Scholar Program [R01HG008150, 5T32HG000044-22]
- NHGRI Institutional Training Grant in Genome Science
- EU IMI program [UE7-DIRECT-115317-1]
- FNS [31003A_149984, DK110919, F32HG009987]
- Massachusetts Lions Eye Research Fund Grant [2R01GM108711, R01MH101820]
- Consolidate Research Group Generalitat de Catalunya [SGR 1736]
- CERCA program
- Rhodes Trust
- Natural Sciences and Engineering Research Council of Canada
- Spanish Ministry of Science, Innovation and Universities
- Centro de Excelencia Severo Ochoa
- CERCA Programme/Generalitat de Catalunya
- Biological Sciences Division at the University of Chicago
- NIH [UL1TR000430]
- [R01MH101814]
- [U01HG007593]
- [R01MH101822]
- [U01HG007598]
- [U01MH104393]
- [R01MH106842]
- [R01HL142028]
- [R01GM122924]
- [R01MH107666]
- [P30DK020595]
- [UM1HG008901]
- [R01GM124486]
- [R01HG010067]
- [R01HG002585]
- Swiss National Science Foundation (SNF) [31003A_149984] Funding Source: Swiss National Science Foundation (SNF)
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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.
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