ArticleNature genetics2020
Quantifying genetic effects on disease mediated by assayed gene expression levels.
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 5 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
214 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Integrating cell-type-specific gene expression and genome-wide associations identifies risk genes for schizophrenia.Molecular psychiatry · 2026Pooled it
- A meta-analysis of single-nucleus expression quantitative trait loci linking genetic risk to brain disorders.Nature genetics · 2026Pooled it
- GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.Nature communications · 2025Pooled it
- Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.Nature human behaviour · 2024Pooled it
- Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function.Communications biology · 2023Pooled it
- Single-nucleus atlas of cell-type specific genetic regulation in the human brain.Nature genetics · 2026Article
- Article
- Machine learning and statistical methods for molecular quantitative trait loci.Nature reviews. Genetics · 2026Review
- Scalable context-dependent single-cell eQTL mapping reveals disease-relevant regulatory variation beyond static models.medRxiv : the preprint server for health sciences · 2026Article
- Identifying independent causal cell types for human diseases and risk variants.Cell genomics · 2026Article
- Tissue-resident immune cells drive genetic risk in autoimmune and lung diseases.Nature immunology · 2026Article
- Post-genome-wide association study variant-to-function challenges in asthma research.The Journal of allergy and clinical immunology · 2026Review
- Where risk resides.Nature immunology · 2026Article
- Article
- Genome-wide pQTL mapping in human skin identifies specific genetic regulators and mechanistic links to skin disorders.Nature communications · 2026Article
- Integrative genetic analysis identifies shared regulation of DNA methylation and gene expression in migraine risk.The journal of headache and pain · 2026Article
- Pangenome-based human genome analysis improves trait association and genomic prediction.bioRxiv : the preprint server for biology · 2026Article
- Co-expression-based models improve eQTL predictions for transcriptome-wide association studies and highlight new schizophrenia-associated genes.Nature genetics · 2026Article
- Trans-regulation of heterochromatin underlies genetic variation in 3D genome contacts in mouse embryonic stem cells.Genome biology · 2026Article
- Regulatory network topology and the genetic architecture of gene expression.Cell genomics · 2026Article
154 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Disease variants identified by genome-wide association studies (GWAS) tend to overlap with expression quantitative trait loci (eQTLs), but it remains unclear whether this overlap is driven by gene expression levels 'mediating' genetic effects on disease. Here, we introduce a new method, mediated expression score regression (MESC), to estimate disease heritability mediated by the cis genetic component of gene expression levels. We applied MESC to GWAS summary statistics for 42 traits (average N = 323,000) and cis-eQTL summary statistics for 48 tissues from the Genotype-Tissue Expression (GTEx) consortium. Averaging across traits, only 11 ± 2% of heritability was mediated by assayed gene expression levels. Expression-mediated heritability was enriched in genes with evidence of selective constraint and genes with disease-appropriate annotations. Our results demonstrate that assayed bulk tissue eQTLs, although disease relevant, cannot explain the majority of disease heritability.
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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.