ArticlePLoS genetics2006
Two-stage two-locus models in genome-wide association.
Article in PLoS genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 3 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.
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
125 citing papers in PubMed, 3 syntheses or guidelines pooled it, 232 citations in OpenAlex.
- A meta-analytic framework for detection of genetic interactions.Genetic epidemiology · 2016Pooled it
- Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis.PloS one · 2013Pooled it
- Ultrafast genome-wide scan for SNP-SNP interactions in common complex disease.Genome research · 2012Pooled it
- A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic interaction effects.Nature genetics · 2025Article
- Article
- Detecting genetic interactions with visible neural networks.Communications biology · 2025Article
- Review on GPU accelerated methods for genome-wide SNP-SNP interactions.Molecular genetics and genomics : MGG · 2024Review
- Genome-wide association and epistasis studies reveal the genetic basis of saline-alkali tolerance at the germination stage in rice.Frontiers in plant science · 2023Article
- Dissecting Complex Traits Using Omics Data: A Review on the Linear Mixed Models and Their Application in GWAS.Plants (Basel, Switzerland) · 2022Review
- Evaluating the detection ability of a range of epistasis detection methods on simulated data for pure and impure epistatic models.PloS one · 2022Article
- Multifactor dimensionality reduction reveals the effect of interaction between ERAP1 and IFIH1 polymorphisms in psoriasis susceptibility genes.Frontiers in genetics · 2022Article
- A parallelized strategy for epistasis analysis based on Empirical Bayesian Elastic Net models.Bioinformatics (Oxford, England) · 2020Article
- Embracing study heterogeneity for finding genetic interactions in large-scale research consortia.Genetic epidemiology · 2020Article
- Association betweenNeural regeneration research · 2019Article
- Identification of epistasis loci underlying rice flowering time by controlling population stratification and polygenic effect.DNA research : an international journal for rapid publication of reports on genes and genomes · 2019Article
- MatrixEpistasis: ultrafast, exhaustive epistasis scan for quantitative traits with covariate adjustment.Bioinformatics (Oxford, England) · 2018Article
- Analysis of two susceptibility SNPs in HLA region and evidence of interaction between rs6457617 in HLA-DQB1 and HLA-DRB1*04 locus on Tunisian rheumatoid arthritis.Journal of genetics · 2017Article
- The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2017Review
- Genetic Association Analysis of Fasting and 1- and 2-Hour Glucose Tolerance Test Data Using a Generalized Index of Dissimilarity Measure for the Korean Population.Genomics & informatics · 2016Article
- Interaction Between Peroxisome Proliferator Activated Receptor δ and Epithelial Membrane Protein 2 Polymorphisms Influences HDL-C Levels in the Chinese Population.Annals of human genetics · 2016Article
65 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 at 2 institutions in 1 country.
Funding
Abstract
Studies in model organisms suggest that epistasis may play an important role in the etiology of complex diseases and traits in humans. With the era of large-scale genome-wide association studies fast approaching, it is important to quantify whether it will be possible to detect interacting loci using realistic sample sizes in humans and to what extent undetected epistasis will adversely affect power to detect association when single-locus approaches are employed. We therefore investigated the power to detect association for an extensive range of two-locus quantitative trait models that incorporated varying degrees of epistasis. We compared the power to detect association using a single-locus model that ignored interaction effects, a full two-locus model that allowed for interactions, and, most important, two two-stage strategies whereby a subset of loci initially identified using single-locus tests were analyzed using the full two-locus model. Despite the penalty introduced by multiple testing, fitting the full two-locus model performed better than single-locus tests for many of the situations considered, particularly when compared with attempts to detect both individual loci. Using a two-stage strategy reduced the computational burden associated with performing an exhaustive two-locus search across the genome but was not as powerful as the exhaustive search when loci interacted. Two-stage approaches also increased the risk of missing interacting loci that contributed little effect at the margins. Based on our extensive simulations, our results suggest that an exhaustive search involving all pairwise combinations of markers across the genome might provide a useful complement to single-locus scans in identifying interacting loci that contribute to moderate proportions of the phenotypic variance.
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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.