The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans¶
Why this mattered¶
TBD
Abstract¶
Expression, genetic variation, and tissues Human genomes show extensive genetic variation across individuals, but we have only just started documenting the effects of this variation on the regulation of gene expression. Furthermore, only a few tissues have been examined per genetic variant. In order to examine how genetic expression varies among tissues within individuals, the Genotype-Tissue Expression (GTEx) Consortium collected 1641 postmortem samples covering 54 body sites from 175 individuals. They identified quantitative genetic traits that affect gene expression and determined which of these exhibit tissue-specific expression patterns. Melé et al. measured how transcription varies among tissues, and Rivas et al. looked at how truncated protein variants affect expression across tissues. Science , this issue p. 648 , p. 660 , p. 666 ; see also p. 640
Related¶
- cite → Statistical significance for genomewide studies — The GTEx pilot uses genome-wide significance principles to evaluate large-scale associations between genetic variants and gene expression.
- cite → The Genotype-Tissue Expression (GTEx) project. — The GTEx pilot is the first multitissue analysis built from the GTEx project's tissue collection and genotype-expression study design.
- cite → Integrative analysis of 111 reference human epigenomes — The GTEx pilot links expression quantitative trait loci to regulatory annotations from reference human epigenomes.
- cite → Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing — The GTEx pilot controls eQTL discovery error rates using the Benjamini-Hochberg false discovery rate framework.
- cite → Mapping and quantifying mammalian transcriptomes by RNA-Seq — The GTEx pilot quantifies tissue-specific gene expression using RNA-seq transcriptome measurement methods.
- cite → Principal components analysis corrects for stratification in genome-wide association studies — The GTEx pilot uses principal components to account for population structure and other latent confounders in association analyses.
- cite → PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses — The GTEx pilot uses PLINK-style genome association tooling for genotype quality control and variant analysis.
- cite → A framework for variation discovery and genotyping using next-generation DNA sequencing data — The GTEx pilot depends on GATK-based variant discovery and genotyping for processing next-generation sequencing data.
- cite → A map of human genome variation from population-scale sequencing — The GTEx pilot uses population-scale human variation maps as reference context for interpreting genetic variants.
- cite → An integrated encyclopedia of DNA elements in the human genome — The GTEx pilot compares eQTLs with ENCODE regulatory elements to interpret noncoding functional effects.
- enables → The GTEx Consortium atlas of genetic regulatory effects across human tissues — The GTEx pilot established multi-tissue eQTL mapping workflows that the 2020 GTEx atlas scaled across many more tissues, samples, and regulatory effect classes.
- cite ← Analysis of protein-coding genetic variation in 60,706 humans — ExAC uses GTEx expression data to help interpret the functional impact of protein-coding variants across human tissues.
- cite ← The GTEx Consortium atlas of genetic regulatory effects across human tissues — The 2020 GTEx atlas expands the 2015 pilot analysis from initial multitissue eQTL mapping to a larger cross-tissue catalog of genetic regulatory effects.
- enables ← Statistical significance for genomewide studies — Genomewide significance thresholds enabled GTEx to interpret large-scale eQTL associations while controlling false positive genetic signals.
- enables ← Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing — False discovery rate control enabled GTEx to report tissue-specific eQTL findings across many genes and variants with multiple-testing correction.
- enables ← Mapping and quantifying mammalian transcriptomes by RNA-Seq — RNA-Seq transcript quantification enabled GTEx to measure gene expression across tissues for eQTL mapping.
- enables ← Principal components analysis corrects for stratification in genome-wide association studies — PCA correction for population stratification enabled GTEx to adjust genotype-expression association tests for ancestry-related confounding.
- enables ← PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses — PLINK enabled GTEx's genome-wide genotype quality control and association testing infrastructure for eQTL analysis.
- enables ← A map of human genome variation from population-scale sequencing — The 1000 Genomes variation map enabled GTEx to use population-scale human variant references for genotype imputation and variant interpretation.