ArticleeLife2016
Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 4 of them syntheses that pooled it.
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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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
77 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Exploring genetic variation that influences brain methylation in attention-deficit/hyperactivity disorder.Translational psychiatry · 2019Pooled it
- Genome-wide association study in two populations to determine genetic variants associated with Toxoplasma gondii infection and relationship to schizophrenia risk.Progress in neuro-psychopharmacology & biological psychiatry · 2019Pooled it
- GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals.Scientific reports · 2017Pooled it
- Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain.Nature genetics · 2026Article
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- Genetically supported drug target prioritization for rare diseases.Genome medicine · 2026Article
- Genomics of drug target prioritization for complex diseases.Nature reviews. Genetics · 2026Review
- Integrative analysis reveals synergistic regulation of Sp7 by BRD9 and Wnt/β-catenin signaling during osteogenic differentiation.Communications biology · 2025Article
- A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress.Genome research · 2025Article
- Analyses of GWAS and Sub-Threshold Loci Lead to the Discovery of Dendrite Development and Morphology Dysfunction Underlying Schizophrenia Genetic Risk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Genetic modulation of lncPSMB1 confers non-syndromic cleft lip with or without cleft palate susceptibility by promoting cell apoptosis.Communications biology · 2025Article
- Genome-wide identification and analysis of recurring patterns of epigenetic variation across individuals.Communications biology · 2025Article
- Seeing more than the Tip of the Iceberg: Approaches to Subthreshold Effects in Functional Magnetic Resonance Imaging of the Brain.Clinical neuroradiology · 2024Review
- Crosstalk between epitranscriptomic and epigenomic modifications and its implication in human diseases.Cell genomics · 2024Article
- Article
- Omics-based construction of regulatory variants can be applied to help decipher pig liver-related traits.Communications biology · 2024Article
- Epigenetic profiling reveals key genes and cis-regulatory networks specific to human parathyroids.Nature communications · 2024Article
- Article
- Causal links of α-thalassemia indices and cardiometabolic traits and diabetes: MR study.Life science alliance · 2023Article
17 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
19 authors.
Funding
Abstract
Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes of these sub-threshold loci, demonstrating that most sub-threshold loci have regulatory consequences and that genetic perturbation of nearby genes causes cardiac phenotypes in mouse. Our work provides a general approach for improving the detection of novel loci associated with complex human traits.
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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.