The GTEx Consortium atlas of genetic regulatory effects across human tissues¶
Why this mattered¶
TBD
Abstract¶
The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.
Related¶
- cite → The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans — The 2020 GTEx atlas expands the 2015 pilot analysis from initial multitissue eQTL mapping to a larger cross-tissue catalog of genetic regulatory effects.
- cite → Statistical significance for genomewide studies — The GTEx atlas uses genomewide significance principles from the 2003 paper to control false positive claims in large-scale genetic association analyses.
- cite → The Genotype-Tissue Expression (GTEx) project. — The GTEx atlas cites the 2013 GTEx project paper as the original design and rationale for systematically mapping human tissue-specific regulatory variation.
- cite → Integrative analysis of 111 reference human epigenomes — The GTEx atlas links eQTLs to the Roadmap Epigenomics reference maps to interpret regulatory variants in tissue-specific chromatin and epigenomic contexts.
- cite → Biological insights from 108 schizophrenia-associated genetic loci — The GTEx atlas uses schizophrenia GWAS loci as an example of how tissue-specific regulatory effects can help interpret disease-associated variants.
- cite → Differential expression analysis for sequence count data — The GTEx atlas cites DESeq as a statistical method for modeling RNA-seq count data in differential expression analyses.
- cite → An integrated encyclopedia of DNA elements in the human genome — The GTEx atlas relates its tissue eQTL maps to ENCODE's functional DNA annotations to prioritize regulatory elements affected by genetic variation.
- cite → The UK Biobank resource with deep phenotyping and genomic data — GTEx cites UK Biobank as a large-scale genotype-linked phenotyping resource that complements GTEx tissue-specific regulatory variant mapping.
- enables ← The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans — The GTEx pilot established multi-tissue eQTL mapping workflows that the 2020 GTEx atlas scaled across many more tissues, samples, and regulatory effect classes.
- enables ← Statistical significance for genomewide studies — The genomewide significance framework enabled GTEx to control false discoveries when testing millions of variant-gene regulatory associations across tissues.
- enables ← The Genotype-Tissue Expression (GTEx) project. — The 2013 GTEx project paper defined the tissue-donor resource and analysis goals that the 2020 atlas realized at full consortium scale.
- enables ← Integrative analysis of 111 reference human epigenomes — The Roadmap Epigenomics reference maps enabled GTEx to interpret tissue-specific eQTLs through chromatin states and regulatory annotations.
- enables ← Biological insights from 108 schizophrenia-associated genetic loci — The schizophrenia GWAS loci study motivated GTEx-style tissue-specific expression regulation analyses for assigning noncoding disease variants to genes and tissues.
- enables ← Differential expression analysis for sequence count data — DESeq's count-based differential expression modeling enabled GTEx analyses of RNA-seq gene expression variation across tissues and samples.
- enables ← An integrated encyclopedia of DNA elements in the human genome — ENCODE's catalog of functional DNA elements enabled GTEx to annotate regulatory variants with promoters, enhancers, and other genomic features.