ArticleNature2014
Detection and replication of epistasis influencing transcription in humans.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 113 papers, 1 of them a synthesis 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- A meta-analytic framework for detection of genetic interactions.Genetic epidemiology · 2016Pooled it
- Quantitative trait loci, G×E and G×G for glycemic traits: response to metformin and placebo in the Diabetes Prevention Program (DPP).Journal of human genetics · 2022Trial
- Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients.Immunology · 2015Trial
- Phantom epistasis through the lens of genealogies.Genetics · 2026Article
- A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic interaction effects.Nature genetics · 2025Article
- Concordance between male- and female-specific GWAS results helps define underlying genetic architecture of complex traits.Nature communications · 2025Article
- Decoding ancestry-specific genetic risk: interpretable deep feature selection reveals prostate cancer SNP disparities in diverse populations.BioData mining · 2025Article
- Performance of deep-learning-based approaches to improve polygenic scores.Nature communications · 2025Article
- Haplotype analysis incorporating ancestral origins identified novel genetic loci associated with chicken body weight using an advanced intercross line.Genetics, selection, evolution : GSE · 2024Article
- A scalable adaptive quadratic kernel method for interpretable epistasis analysis in complex traits.Genome research · 2024Article
- Article
- Factorizing polygenic epistasis improves prediction and uncovers biological pathways in complex traits.American journal of human genetics · 2023Article
- Fast kernel-based association testing of non-linear genetic effects for biobank-scale data.Nature communications · 2023Article
- Parent-offspring genotyped trios unravelling genomic regions with gametic and genotypic epistatic transmission bias on the cattle genome.Frontiers in genetics · 2023Article
- Article
- Dissecting Complex Traits Using Omics Data: A Review on the Linear Mixed Models and Their Application in GWAS.Plants (Basel, Switzerland) · 2022Review
- Non-linear machine learning models incorporating SNPs and PRS improve polygenic prediction in diverse human populations.Communications biology · 2022Article
- Concurrent outcomes from multiple approaches of epistasis analysis for human body mass index associated loci provide insights into obesity biology.Scientific reports · 2022Article
- Interpretable network-guided epistasis detection.GigaScience · 2022Article
- Detecting gene-gene interactions from GWAS using diffusion kernel principal components.BMC bioinformatics · 2022Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2021-08-11Error in Analyses ·
- Commented on by
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- Retracted
Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
Epistasis is the phenomenon whereby one polymorphism's effect on a trait depends on other polymorphisms present in the genome. The extent to which epistasis influences complex traits and contributes to their variation is a fundamental question in evolution and human genetics. Although often demonstrated in artificial gene manipulation studies in model organisms, and some examples have been reported in other species, few examples exist for epistasis among natural polymorphisms in human traits. Its absence from empirical findings may simply be due to low incidence in the genetic control of complex traits, but an alternative view is that it has previously been too technically challenging to detect owing to statistical and computational issues. Here we show, using advanced computation and a gene expression study design, that many instances of epistasis are found between common single nucleotide polymorphisms (SNPs). In a cohort of 846 individuals with 7,339 gene expression levels measured in peripheral blood, we found 501 significant pairwise interactions between common SNPs influencing the expression of 238 genes (P < 2.91 × 10(-16)). Replication of these interactions in two independent data sets showed both concordance of direction of epistatic effects (P = 5.56 × 10(-31)) and enrichment of interaction P values, with 30 being significant at a conservative threshold of P < 9.98 × 10(-5). Forty-four of the genetic interactions are located within 5 megabases of regions of known physical chromosome interactions (P = 1.8 × 10(-10)). Epistatic networks of three SNPs or more influence the expression levels of 129 genes, whereby one cis-acting SNP is modulated by several trans-acting SNPs. For example, MBNL1 is influenced by an additive effect at rs13069559, which itself is masked by trans-SNPs on 14 different chromosomes, with nearly identical genotype-phenotype maps for each cis-trans interaction. This study presents the first evidence, to our knowledge, for many instances of segregating common polymorphisms interacting to influence 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.