genetic epistasis


Summary: A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.

Top Publications

  1. Alcázar R, García A, Parker J, Reymond M. Incremental steps toward incompatibility revealed by Arabidopsis epistatic interactions modulating salicylic acid pathway activation. Proc Natl Acad Sci U S A. 2009;106:334-9 pubmed publisher
    ..This could allow the accumulation of additional incompatibilities before reaching complete reproductive isolation. ..
  2. Greene C, Penrod N, Williams S, Moore J. Failure to replicate a genetic association may provide important clues about genetic architecture. PLoS ONE. 2009;4:e5639 pubmed publisher
    ..We recommend that polymorphisms that fail to replicate be checked for interactions with other polymorphisms, particularly when samples are collected from groups with distinct ethnic backgrounds or different geographic regions. ..
  3. Wu J, Devlin B, Ringquist S, Trucco M, Roeder K. Screen and clean: a tool for identifying interactions in genome-wide association studies. Genet Epidemiol. 2010;34:275-85 pubmed publisher
    ..When the method is applied to data obtained from the Wellcome Trust Case Control Consortium study of Type 1 Diabetes it uncovers evidence supporting interaction within the HLA class II region as well as within Chromosome 12q24. ..
  4. Emily M, Mailund T, Hein J, Schauser L, Schierup M. Using biological networks to search for interacting loci in genome-wide association studies. Eur J Hum Genet. 2009;17:1231-40 pubmed publisher
  5. Jiang R, Tang W, Wu X, Fu W. A random forest approach to the detection of epistatic interactions in case-control studies. BMC Bioinformatics. 2009;10 Suppl 1:S65 pubmed publisher
  6. Branicki W, Brudnik U, Wojas Pelc A. Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype. Ann Hum Genet. 2009;73:160-70 pubmed publisher
    ..Finally, using various approaches we were able to show that there is an interaction between MC1R and HERC2 in determination of skin and hair colour in the studied population sample. ..
  7. Wu X, Blake S, Sleper D, Shannon J, Cregan P, Nguyen H. QTL, additive and epistatic effects for SCN resistance in PI 437654. Theor Appl Genet. 2009;118:1093-105 pubmed publisher
    ..Several minor QTLs on LGs-C1, D1a, H, and K were also found to be associated with SCN resistance. Confirmation of the new resistance QTL is underway by evaluating another RIL population with a different genetic background. ..
  8. Tang X, Guo S, Sun H, Song X, Jiang Z, Sheng L, et al. Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population. Pharmacogenet Genomics. 2009;19:345-52 pubmed
    ..4, 95% CI=4.5-52.5). These findings suggested a substantial influence of CYP2A6 polymorphism as well as the interaction with MAOA resulting in risk modulation on smoking behavior in Chinese male population. ..
  9. Burger R. Multilocus selection in subdivided populations II. Maintenance of polymorphism under weak or strong migration. J Math Biol. 2009;58:979-97 pubmed publisher
    ..Thus, several scenarios are identified under which multilocus polymorphism can be maintained by migration-selection balance when this is impossible in a panmictic population. ..

Scientific Experts

More Information


  1. Kliebenstein D. Advancing genetic theory and application by metabolic quantitative trait loci analysis. Plant Cell. 2009;21:1637-46 pubmed publisher
    ..Additionally, the review describes how new observations from metabolic QTL mapping analyses are helping to shape and expand the concepts of genetic epistasis.
  2. Ulitsky I, Krogan N, Shamir R. Towards accurate imputation of quantitative genetic interactions. Genome Biol. 2009;10:R140 pubmed publisher
    ..Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions. We also present data on almost 190,000 novel interactions. ..
  3. Burger R. Polymorphism in the two-locus Levene model with nonepistatic directional selection. Theor Popul Biol. 2009;76:214-28 pubmed publisher
    ..If the favorable allele is (partially) dominant in its deme, more than 20% of all parameter combinations lead to a globally asymptotically stable, fully polymorphic equilibrium. ..
  4. Wan X, Yang C, Yang Q, Xue H, Tang N, Yu W. Predictive rule inference for epistatic interaction detection in genome-wide association studies. Bioinformatics. 2010;26:30-7 pubmed publisher
    ..Our results indicate that finding epistatic interactions in GWAS is computationally attainable in practice. ..
  5. Gutierrez Gonzalez J, Wu X, Zhang J, Lee J, Ellersieck M, Shannon J, et al. Genetic control of soybean seed isoflavone content: importance of statistical model and epistasis in complex traits. Theor Appl Genet. 2009;119:1069-83 pubmed publisher
  6. McGovern D, Rotter J, Mei L, Haritunians T, Landers C, Derkowski C, et al. Genetic epistasis of IL23/IL17 pathway genes in Crohn's disease. Inflamm Bowel Dis. 2009;15:883-9 pubmed publisher
    ..Inflamm Bowel Dis 2009). ..
  7. Mair W, Panowski S, Shaw R, Dillin A. Optimizing dietary restriction for genetic epistasis analysis and gene discovery in C. elegans. PLoS ONE. 2009;4:e4535 pubmed publisher
    ..1, highlighting the importance of first optimizing DR to identify universal regulators of DR mediated longevity. ..
  8. Greene C, Sinnott Armstrong N, Himmelstein D, Park P, Moore J, Harris B. Multifactor dimensionality reduction for graphics processing units enables genome-wide testing of epistasis in sporadic ALS. Bioinformatics. 2010;26:694-5 pubmed publisher
    ..MDRGPU is open source and available free of charge from ..
  9. Tyler A, Asselbergs F, Williams S, Moore J. Shadows of complexity: what biological networks reveal about epistasis and pleiotropy. Bioessays. 2009;31:220-7 pubmed publisher
    ..Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena. ..
  10. Jonikas M, Collins S, Denic V, Oh E, Quan E, Schmid V, et al. Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum. Science. 2009;323:1693-7 pubmed publisher
    ..The use of a quantitative reporter in a comprehensive screen followed by systematic analysis of genetic dependencies should be broadly applicable to functional dissection of complex cellular processes from yeast to human. ..
  11. Combarros O, van Duijn C, Hammond N, Belbin O, Arias Vasquez A, Cortina Borja M, et al. Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease. J Neuroinflammation. 2009;6:22 pubmed publisher
    ..We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD. ..
  12. Cordell H. Detecting gene-gene interactions that underlie human diseases. Nat Rev Genet. 2009;10:392-404 pubmed publisher
    ..I also discuss the difficulties in determining the biological relevance of statistical interactions. ..
  13. Nagylaki T. Evolution under the multilocus Levene model without epistasis. Theor Popul Biol. 2009;76:197-213 pubmed publisher
    ..e., deme independent), then every uniform selection equilibrium is a migration-selection equilibrium and generically has the same stability as under pure selection. ..
  14. Edwards T, Pericak Vance M, Gilbert J, Haines J, Martin E, Ritchie M. An association analysis of Alzheimer disease candidate genes detects an ancestral risk haplotype clade in ACE and putative multilocus association between ACE, A2M, and LRRTM3. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:721-35 pubmed publisher
  15. de Visser J, Park S, Krug J. Exploring the effect of sex on empirical fitness landscapes. Am Nat. 2009;174 Suppl 1:S15-30 pubmed publisher
    ..We discuss possible reasons for the discrepancy between our results and the reports of faster adaptation of sexual populations. ..
  16. Edwards T, Lewis K, Velez D, Dudek S, Ritchie M. Exploring the performance of Multifactor Dimensionality Reduction in large scale SNP studies and in the presence of genetic heterogeneity among epistatic disease models. Hum Hered. 2009;67:183-92 pubmed publisher
    ..A study in which a population with high heritability estimates is sampled predisposes the MDR study to success more than a larger ascertainment in a population with smaller estimates. ..
  17. Shao H, Burrage L, Sinasac D, Hill A, Ernest S, O BRIEN W, et al. Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis. Proc Natl Acad Sci U S A. 2008;105:19910-4 pubmed publisher
    ..These results have implications for identification of complex trait genes, developmental and physiological studies of phenotypic variation, and opportunities to engineer phenotypic outcomes in complex biological systems...
  18. Ghandilyan A, Barboza L, Tisné S, Granier C, Reymond M, Koornneef M, et al. Genetic analysis identifies quantitative trait loci controlling rosette mineral concentrations in Arabidopsis thaliana under drought. New Phytol. 2009;184:180-92 pubmed publisher
    ..The low number of common mineral concentration QTLs, shared among different RIL populations, tissues and conditions in Arabidopsis, suggests that breeding for robust, mineral biofortified crops will be complex. ..
  19. Hnisz D, Schwarzmüller T, Kuchler K. Transcriptional loops meet chromatin: a dual-layer network controls white-opaque switching in Candida albicans. Mol Microbiol. 2009;74:1-15 pubmed publisher
    ..Our observations postulate that chromatin modifications may serve as a means to integrate environmental or host stimuli through the underlying transcriptional circuits to determine cell fate in C. albicans. ..
  20. Hu G, Wang S, Wang Z, Li Y, Li H. Genetic epistasis analysis of 10 peroxisome proliferator-activated receptor ?-correlated genes in broiler lines divergently selected for abdominal fat content. Poult Sci. 2010;89:2341-50 pubmed publisher
    ..Our results suggest that C/EBP? c.552G>A might be the most important locus contributing to phenotypic variation in AFW among all the polymorphisms detected in this study. ..
  21. Yang C, He Z, Wan X, Yang Q, Xue H, Yu W. SNPHarvester: a filtering-based approach for detecting epistatic interactions in genome-wide association studies. Bioinformatics. 2009;25:504-11 pubmed publisher
    .. ..
  22. Ma L, Runesha H, Dvorkin D, Garbe J, Da Y. Parallel and serial computing tools for testing single-locus and epistatic SNP effects of quantitative traits in genome-wide association studies. BMC Bioinformatics. 2008;9:315 pubmed publisher
  23. Le Meur N, Gentleman R. Modeling synthetic lethality. Genome Biol. 2008;9:R135 pubmed publisher
    ..Our model in conjunction with applied statistical methods and computational methods provides new tools to better characterize synthetic genetic interactions. ..
  24. Sanjuan R, Nebot M. A network model for the correlation between epistasis and genomic complexity. PLoS ONE. 2008;3:e2663 pubmed publisher
  25. Roguev A, Bandyopadhyay S, Zofall M, Zhang K, Fischer T, Collins S, et al. Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast. Science. 2008;322:405-10 pubmed publisher
    ..Hence, conservation occurs at the level of the functional module (protein complex), but the genetic cross talk between modules can differ substantially. ..
  26. Phillips P. Epistasis--the essential role of gene interactions in the structure and evolution of genetic systems. Nat Rev Genet. 2008;9:855-67 pubmed publisher
  27. Pattin K, White B, Barney N, Gui J, Nelson H, Kelsey K, et al. A computationally efficient hypothesis testing method for epistasis analysis using multifactor dimensionality reduction. Genet Epidemiol. 2009;33:87-94 pubmed publisher
    ..We then demonstrate this new method by applying it to a genetic epidemiology study of bladder cancer susceptibility that was previously analyzed using MDR and assessed using a 1,000-fold permutation test. ..
  28. Pu S, Ronen K, Vlasblom J, Greenblatt J, Wodak S. Local coherence in genetic interaction patterns reveals prevalent functional versatility. Bioinformatics. 2008;24:2376-83 pubmed publisher
    ..Our algorithm hence represents a valuable tool for uncovering new roles for genes with annotated functions and for mapping groups of genes and proteins into pathways. ..
  29. Michel J, Yeh P, Chait R, Moellering R, Kishony R. Drug interactions modulate the potential for evolution of resistance. Proc Natl Acad Sci U S A. 2008;105:14918-23 pubmed publisher
    ..This framework reveals the central role of drug epistasis in the evolution of resistance and points to new strategies for combating the emergence of drug-resistant bacteria. ..
  30. Meyer D, Bailis A. Telomerase deficiency affects the formation of chromosomal translocations by homologous recombination in Saccharomyces cerevisiae. PLoS ONE. 2008;3:e3318 pubmed publisher
    ..Thus, telomerase may exert a substantial effect on global genome stability, which may bear significantly on the appearance and progression of cancer in humans. ..
  31. Calle M, Urrea V, Vellalta G, Malats N, Steen K. Improving strategies for detecting genetic patterns of disease susceptibility in association studies. Stat Med. 2008;27:6532-46 pubmed publisher
  32. Burger R. Multilocus selection in subdivided populations I. Convergence properties for weak or strong migration. J Math Biol. 2009;58:939-78 pubmed publisher
    ..In both cases, every trajectory converges to an equilibrium, thus no cycling or complicated dynamics can occur. ..
  33. Gayan J, Gonzalez Perez A, Bermudo F, Saez M, Royo J, Quintas A, et al. A method for detecting epistasis in genome-wide studies using case-control multi-locus association analysis. BMC Genomics. 2008;9:360 pubmed publisher
    ..With the current availability of genetic studies with large numbers of individuals and genetic markers, HFCC can have a great impact in the identification of epistatic effects that escape the standard single-locus association analyses. ..
  34. Gao H, Granka J, Feldman M. On the classification of epistatic interactions. Genetics. 2010;184:827-37 pubmed publisher
    ..We anticipate that our method will improve detection of epistatic interactions and will help to unravel the mysteries of complex biological systems. ..
  35. Flowers E, Poole R, Tursun B, Bashllari E, Pe er I, Hobert O. The Groucho ortholog UNC-37 interacts with the short Groucho-like protein LSY-22 to control developmental decisions in C. elegans. Development. 2010;137:1799-805 pubmed publisher
    ..We propose that Groucho-mediated gene regulatory events involve heteromeric complexes of distinct Groucho-like proteins. ..
  36. Jagomagi T, Nikopensius T, Krjutskov K, Tammekivi V, Viltrop T, Saag M, et al. MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate. Eur J Oral Sci. 2010;118:213-20 pubmed publisher
    ..This study provides further evidence implicating MSX1 and MTHFR in the etiology of nonsyndromic CL/P across different populations...
  37. de Cid R, Riveira Munoz E, Zeeuwen P, Robarge J, Liao W, Dannhauser E, et al. Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet. 2009;41:211-5 pubmed publisher
    ..LCE expression can be induced in normal epidermis by skin barrier disruption and is strongly expressed in psoriatic lesions, suggesting that compromised skin barrier function has a role in psoriasis susceptibility. ..
  38. Erturk Hasdemir D, Broemer M, Leulier F, Lane W, Paquette N, Hwang D, et al. Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes. Proc Natl Acad Sci U S A. 2009;106:9779-84 pubmed publisher
    ..Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish. ..
  39. Manichaikul A, Moon J, Sen S, Yandell B, Broman K. A model selection approach for the identification of quantitative trait loci in experimental crosses, allowing epistasis. Genetics. 2009;181:1077-86 pubmed publisher
    ..We illustrate the use of our model selection criteria as exploratory tools; simulation studies demonstrate reasonable power to detect QTL. Our liberal criterion is comparable in power to two Bayesian approaches. ..
  40. Koller D, Liu L, Alam I, Sun Q, Econs M, Foroud T, et al. Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2 rats. Mamm Genome. 2009;20:180-6 pubmed publisher
  41. Schmidt Küntzel A, Nelson G, David V, Schäffer A, Eizirik E, Roelke M, et al. A domestic cat X chromosome linkage map and the sex-linked orange locus: mapping of orange, multiple origins and epistasis over nonagouti. Genetics. 2009;181:1415-25 pubmed publisher
    ..5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level. ..
  42. Bridgham J, Ortlund E, Thornton J. An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature. 2009;461:515-9 pubmed publisher
    ..Our findings indicate that even if selection for the ancestral function were imposed, direct reversal would be extremely unlikely, suggesting an important role for historical contingency in protein evolution. ..
  43. Beebe K, Lee W, Micchelli C. JAK/STAT signaling coordinates stem cell proliferation and multilineage differentiation in the Drosophila intestinal stem cell lineage. Dev Biol. 2010;338:28-37 pubmed publisher
  44. Ball L, Zhang K, Cobb J, Boone C, Xiao W. The yeast Shu complex couples error-free post-replication repair to homologous recombination. Mol Microbiol. 2009;73:89-102 pubmed publisher
    ..This mechanism appears to be conserved throughout eukaryotes. ..
  45. Tazib T, Ikka T, Kuroda K, Kobayashi Y, Kimura K, Koyama H. Quantitative trait loci controlling resistance to cadmium rhizotoxicity in two recombinant inbred populations of Arabidopsis thaliana are partially shared by those for hydrogen peroxide resistance. Physiol Plant. 2009;136:395-406 pubmed publisher
    ..These data, along with a multitraits QTL analysis in both sets of RILs, suggest that peroxide damage depends on the genotype at a major Cd-tolerant locus on the upper part of chromosome 5. ..
  46. Genevet A, Wehr M, Brain R, Thompson B, Tapon N. Kibra is a regulator of the Salvador/Warts/Hippo signaling network. Dev Cell. 2010;18:300-8 pubmed publisher
    ..We suggest that Kibra is part of an apical scaffold that promotes SWH pathway activity. ..
  47. Bhattacharjee S, Wang Z, Ciampa J, Kraft P, Chanock S, Yu K, et al. Using principal components of genetic variation for robust and powerful detection of gene-gene interactions in case-control and case-only studies. Am J Hum Genet. 2010;86:331-42 pubmed publisher
  48. Han B, Park M, Chen X. A Markov blanket-based method for detecting causal SNPs in GWAS. BMC Bioinformatics. 2010;11 Suppl 3:S5 pubmed publisher
    ..Given the huge size of genomic dataset produced by GWAS, this is critical in saving the potential costs of biological experiments and being an efficient guideline for pathogenesis research. ..
  49. Venancio T, Balaji S, Geetha S, Aravind L. Robustness and evolvability in natural chemical resistance: identification of novel systems properties, biochemical mechanisms and regulatory interactions. Mol Biosyst. 2010;6:1475-91 pubmed publisher
    ..Further, we find evidence that cellular exploration of survival strategies under chemical stress and secondary metabolism draw from a common pool of biochemical players (e.g. acetyltransferases and a novel NTN hydrolase). ..
  50. Guo J, Tian D, McKinney B, Hartman J. Recursive expectation-maximization clustering: a method for identifying buffering mechanisms composed of phenomic modules. Chaos. 2010;20:026103 pubmed publisher
    ..It facilitates identification of phenomic modules, which contribute to buffering mechanisms that underlie cellular homeostasis and the regulation of phenotypic expression. ..
  51. Chevin L, Bastide H, Montchamp Moreau C, Hospital F. Molecular signature of epistatic selection: interrogating genetic interactions in the sex-ratio meiotic drive of Drosophila simulans. Genet Res (Camb). 2009;91:171-82 pubmed publisher
  52. Poole E, Hsu L, Xiao L, Kulmacz R, Carlson C, Rabinovitch P, et al. Genetic variation in prostaglandin E2 synthesis and signaling, prostaglandin dehydrogenase, and the risk of colorectal adenoma. Cancer Epidemiol Biomarkers Prev. 2010;19:547-57 pubmed publisher
    ..These data provide little support for associations between adenoma risk and genetic variability related to PGE(2), yet suggest gene-environment interactions with anti-inflammatory exposures. ..
  53. Huang X, Schmitt J, Dorn L, Griffith C, Effgen S, Takao S, et al. The earliest stages of adaptation in an experimental plant population: strong selection on QTLS for seed dormancy. Mol Ecol. 2010;19:1335-51 pubmed publisher
    ..Genes associated with the ability to arrest development at early life stages and assess environmental conditions are thereby likely targets of intense natural selection early in the colonization process. ..