ArticleCell genomics2026
Buffering of gene dosage response curves for human complex traits.
Article in Cell genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- dubTAGs enable on-demand stabilization for tunable and reversible control of endogenous protein levels.bioRxiv : the preprint server for biology · 2026Article
- Genetic architectures of brain-related traits are shaped by strong selective constraints.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Allele frequencies at recessive disease genes are mainly determined by pleiotropic effects in heterozygotes.Genetics · 2026Article
- Determinants of functional burden pleiotropy and gene dosage responses across human traits.Nature communications · 2026Article
- Gene dosage differences and non-linear impacts on complex traits.Cell genomics · 2026Article
- Combinatorial effects of gene dosage, polygenic background and environment on complex traits.medRxiv : the preprint server for health sciences · 2026Article
- Genetic architectures of brain-related traits are shaped by strong selective constraints.bioRxiv : the preprint server for biology · 2026Article
- Representation in genetic studies affects inference about genetic architecture.bioRxiv : the preprint server for biology · 2026Article
- Semiparametric efficient estimation of small genetic effects in large-scale population cohorts.Biostatistics (Oxford, England) · 2025Article
- Article
- Human-specific gene expansions contribute to brain evolution.bioRxiv : the preprint server for biology · 2025Article
- Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq.bioRxiv : the preprint server for biology · 2025Article
- Specificity, length, and luck: How genes are prioritized by rare and common variant association studies.bioRxiv : the preprint server for biology · 2024Article
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6 authors.
Funding
Abstract
The genome-wide burdens of deletions, loss-of-function mutations, and duplications correlate with many traits. Curiously, for most of these traits, variants that decrease expression have the same genome-wide average direction of effect as variants that increase expression. This seemingly contradicts the intuition that for individual genes, reducing expression should have the opposite effect on a phenotype as increasing expression. To understand this paradox, we use the gene dosage response curve (GDRC), which relates changes in gene expression to expected changes in phenotype. We show that, for many traits, GDRCs are systematically biased in one trait direction relative to the other, a phenomenon we call trait buffering. Because of trait buffering, traits are more easily modified in one direction than the other by genetic variation. We develop a simple theoretical model that explains this bias in trait direction. Our results have broad implications for complex traits, drug discovery, and statistical genetics.
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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.