Previous studies have reported widespread sex-biased gene expression ( 10– 12) and described breast as the most sex-differentiated tissue ( 10, 11, 13). We discovered a total of 13,294 differentially expressed genes, with 473 to 4558 genes discovered per tissue, representing 1.3% to 12.9% of all tested genes, respectively ( Fig. We next modeled sex bias effects across tissues.
Consequently, we are able to identify sex-biased gene expression that does not derive from sex differences in cell type abundances. For each tissue, we first fit a linear model that accounts for known sample and donor characteristics, as well as surrogate variables that capture hidden technical or biological factors of expression variability, including tissue cell type composition (fig. We considered a total of 35,431 X-linked and autosomal genes, including protein coding, long intergenic noncoding RNA (lincRNA), and other less-characterized gene types such as transcribed pseudogenes ( 9).
Using GTEx v8 data (table S1), we quantified sex-biased gene expression in each of the 44 tissue sources for all genes expressed in at least one tissue. By integrating data from genome-wide association studies (GWASs), we report multiple sex-differentiated genetic effects on the transcriptome that colocalize with complex trait associations, highlighting the power of characterizing sex bias in GTEx samples for the mechanistic interpretation of GWAS signals.
#ELIZA ONG AGE 2020 DRIVERS#
By incorporating the results of these sex-aware analyses of GTEx data with gene features and transcription factor binding annotation, we describe tissue-specific and tissue-nonspecific drivers and mechanisms contributing to sex differences in the human transcriptome and eQTLs. We quantify and characterize sex differences in gene expression levels (sex-biased gene expression) and cis sex‐biased expression quantitative trait loci (sb-eQTLs). We present an extensive characterization of sex differences in the human transcriptome across 44 tissue sources of the GTEx project from 838 individuals (557 males, 281 females), constituting a large collection of multi-tissue bulk gene expression and genotype data ( Fig. Because the causative tissue is unknown for many diseases and disorders, analysis of this diverse tissue set can serve as a powerful resource for investigations into the basis of sex-differentiated phenotypes. The analyses presented here characterize sex differences in a relatively large population sample, including many tissues that generally lack characterization. The Genotype-Tissue Expression (GTEx) project ( 7) provides an opportunity to investigate the prevalence and genetic mechanisms of sex differences in transcriptomes and to identify how sex and genetics interact to influence complex traits and disease. These sex differences have been variously attributed to hormones, sex chromosomes, genotype × sex effects, differences in behavior, and differences in environmental exposures ( 6), but the mechanisms and underlying biology of the sex differences remain largely unknown. Many complex human phenotypes, such as anthropometric traits (e.g., waist-to-hip ratio), exhibit sex-differentiated distributions disease features such as prevalence, progression, age of onset, and response to treatment often differ by sex ( 1– 5). These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation. 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. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. 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). However, the molecular mechanisms underlying these differences remain largely unknown. Many complex human phenotypes exhibit sex-differentiated characteristics. Battle, Tuuli Lappalainen, Roderic Guigó, and Barbara E. Pierce, Matthew Stephens, Eleazar Eskin, Emmanouil T.
Hamel, Angel Martinez-Perez, José Manuel Soria, GTEx Consortium §, Brandon L. Gamazon, Anthony Payne, Rodrigo Bonazzola, Alvaro N. Skol, Diego Garrido-Martín, Ferran Reverter, Andrew Brown, Patrick Evans, Eric R. Castel, Pejman Mohammadi, François Aguet, Yuxin Zou, Ekaterina A. Cotter, Princy Parsana, … Show All …, Silva Kasela, Brunilda Balliu, Ana Viñuela, Stephane E. Meritxell Oliva, Manuel Muñoz-Aguirre, Sarah Kim-Hellmuth, Valentin Wucher, Ariel D.
0 kommentar(er)
