ArticleNature2017
The impact of rare variation on gene expression across tissues.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
163 citing papers in PubMed, 289 citations in OpenAlex.
- Machine learning and statistical methods for molecular quantitative trait loci.Nature reviews. Genetics · 2026Review
- Alternative tandem transcription initiation links noncoding variants to human disease through translational control.Nature communications · 2026Article
- Uncultured Amniocytes Enable Rapid and Clinically Informative Prenatal RNA Sequencing for Genetic Diagnosis.International journal of molecular sciences · 2026Article
- Genetic and health determinants of cancer risk in Bangladeshi and Pakistani individuals in the UK.Nature communications · 2026Article
- Population-scale detection of methylation outliers from long-read genome sequencing.medRxiv : the preprint server for health sciences · 2026Article
- Paired DNA and RNA sequencing uncovers common and rare variation regulating human retinal gene expression.Nature communications · 2026Article
- Decoding the enhancer-driven regulatory network for lactoferrin across mammalian species.Zoological research · 2026Article
- Tissue-specific gene dosage disruption is a key feature and pathogenic mechanism of structural variants in the human genome.Genome medicine · 2026Article
- Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation.Science advances · 2026Article
- Admixture-driven structural variation diversity and its functional implications.National science review · 2026Article
- ASTWAS: modeling alternative polyadenylation and SNP effects in kernel-driven TWAS reveal novel genetic associations for complex traits.Briefings in bioinformatics · 2026Article
- CellSNVReg: a multidimensional resource for SNV-mediated regulatory perturbations in single-cell and spatial omics.Nucleic acids research · 2026Article
- Article
- Transcriptome-wide outlier approach identifies individuals with minor spliceopathies.American journal of human genetics · 2025Article
- Impact of polymorphisms on gene expression and splicing in response to exercise and diet-induced weight loss in human skeletal muscle tissues.Cell genomics · 2025Article
- Antisense oligonucleotide depletion ofmedRxiv : the preprint server for health sciences · 2025Article
- Bayesian estimation of allele-specific expression in the presence of phasing uncertainty.Bioinformatics (Oxford, England) · 2025Article
- Genetic regulation of lncRNA expression in whole human brain and their contribution to CNS disorders.Briefings in bioinformatics · 2025Article
- Aberrant gene expression prediction across human tissues.Nature communications · 2025Article
- High performance imputation of structural and single nucleotide variants using low-coverage whole genome sequencing.Genetics, selection, evolution : GSE · 2025Article
103 more citing papers are in PubMed but not listed here.
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Authors and funding
34 authors at 4 institutions in 1 country.
Funding
Abstract
Rare genetic variants are abundant in humans and are expected to contribute to individual disease risk. While genetic association studies have successfully identified common genetic variants associated with susceptibility, these studies are not practical for identifying rare variants. Efforts to distinguish pathogenic variants from benign rare variants have leveraged the genetic code to identify deleterious protein-coding alleles, but no analogous code exists for non-coding variants. Therefore, ascertaining which rare variants have phenotypic effects remains a major challenge. Rare non-coding variants have been associated with extreme gene expression in studies using single tissues, but their effects across tissues are unknown. Here we identify gene expression outliers, or individuals showing extreme expression levels for a particular gene, across 44 human tissues by using combined analyses of whole genomes and multi-tissue RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project v6p release. We find that 58% of underexpression and 28% of overexpression outliers have nearby conserved rare variants compared to 8% of non-outliers. Additionally, we developed RIVER (RNA-informed variant effect on regulation), a Bayesian statistical model that incorporates expression data to predict a regulatory effect for rare variants with higher accuracy than models using genomic annotations alone. Overall, we demonstrate that rare variants contribute to large gene expression changes across tissues and provide an integrative method for interpretation of rare variants in individual genomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.