ReviewWiley interdisciplinary reviews. Systems biology and medicine
Layers of epistasis: genome-wide regulatory networks and network approaches to genome-wide association studies.
Review in Wiley interdisciplinary reviews. Systems biology and medicine. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pathway-based genetic analysis of preterm birth.Genomics · 2013Pooled it
- Leveraging epigenomics and contactomics data to investigate SNP pairs in GWAS.Human genetics · 2018Article
- Leveraging putative enhancer-promoter interactions to investigate two-way epistasis in Type 2 Diabetes GWAS.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2018Article
- Grid-based stochastic search for hierarchical gene-gene interactions in population-based genetic studies of common human diseases.BioData mining · 2017Article
- Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?Carcinogenesis · 2015Review
- Yeast Phenomics: An Experimental Approach for Modeling Gene Interaction Networks that Buffer Disease.Genes · 2015Article
- Heuristic identification of biological architectures for simulating complex hierarchical genetic interactions.Genetic epidemiology · 2015Article
- Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in Communities study.Human genetics · 2014Article
- Genomic analyses with biofilter 2.0: knowledge driven filtering, annotation, and model development.BioData mining · 2013Article
- Should evolutionary geneticists worry about higher-order epistasis?Current opinion in genetics & development · 2013Review
- Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review.Pharmacology & therapeutics · 2013Review
- Approaching "phantom heritability" in psychiatry by hypothesis-driven gene-gene interactions.Frontiers in human neuroscience · 2013Article
- Cancer heterogeneity: origins and implications for genetic association studies.Trends in genetics : TIG · 2012Article
- Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus.Genome research · 2012Article
- Gene ontology analysis of pairwise genetic associations in two genome-wide studies of sporadic ALS.BioData mining · 2012Article
- Pathway analysis of genomic data: concepts, methods, and prospects for future development.Trends in genetics : TIG · 2012Review
- Systems genetics for drug target discovery.Trends in pharmacological sciences · 2011Review
- Mining the diseasome.BioData mining · 2011Article
- Analysis of gene-gene interactions.Current protocols in human genetics · 2011Article
- Mining beyond the exome.BioData mining · 2011Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The conceptual foundation of the genome-wide association study (GWAS) has advanced unchecked since its conception. A revision might seem premature as the potential of GWAS has not been fully realized. Multiple technical and practical limitations need to be overcome before GWAS can be fairly criticized. But with the completion of hundreds of studies and a deeper understanding of the genetic architecture of disease, warnings are being raised. The results compiled to date indicate that risk-associated variants lie predominantly in noncoding regions of the genome. Additionally, alternative methodologies are uncovering large and heterogeneous sets of rare variants underlying disease. The fear is that, even in its fulfillment, the current GWAS paradigm might be incapable of dissecting all kinds of phenotypes. In the following text, we review several initiatives that aim to overcome these limitations. The overarching theme of these studies is the inclusion of biological knowledge to both the analysis and interpretation of genotyping data. GWAS is uninformed of biology by design and although there is some virtue in its simplicity, it is also its most conspicuous deficiency. We propose a framework in which to integrate these novel approaches, both empirical and theoretical, in the form of a genome-wide regulatory network (GWRN). By processing experimental data into networks, emerging data types based on chromatin immunoprecipitation are made computationally tractable. This will give GWAS re-analysis efforts the most current and relevant substrates, and root them firmly on our knowledge of human disease.
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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.