Epistasis is the biological interaction between two or more genes to determine a phenotype. Until relatively recently, there has been confusion in its definition arising from many mathematical and other models not necessarily reflecting biological reality, and underestimation of both its importance in mapping results for complex disease and its potential role in the results of evolutionary genetics.

Keywords: epistasis; evolution; population genetics; complex disease; association tests; quantitative trait loci


Bürger R (2000) The Mathematical Theory of Selection, Recombination, and Mutation. Chichester, UK: John Wiley.

Cordell HJ, Todd JA, Hill NJ, et al. (2001) Statistical modeling of interlocus interactions in a complex disease: rejection of the multiplicative model of epistasis in type 1 diabetes. Genetics 158: 357–367.

Cox NJ, Frigge M, Nicolae DL, et al. (1999) Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans. Nature Genetics 21: 213–215.

Culverhouse R, Suarez BK, Lin J and Reich T (2002) A perspective on epistasis: limits of models displaying no main effect. American Journal of Human Genetics 70: 461–471.

Hartman JL IV, Garvik B and Hartwell L (2001) Principles for the buffering of genetic variation. Science 291: 1001–1004.

Nagel RL (2001) Pleiotropic and epistatic effects in sickle cell anemia. Current Opinion in Hematology 8: 105–110.

Rédei GP (1998) Genetics Manual. Singapore: World Scientific.

Ritchie MD, Hahn LW, Roodi N, et al. (2001) Multifactor‐dimensionality reduction reveals high‐order interactions among estrogen‐metabolism genes in sporadic breast cancer. American Journal of Human Genetics 69: 138–147.

Wilson SR (2001) Epistasis and its possible effects on transmission disequilibrium tests. Annals of Human Genetics 65: 565–575.

Wolf JB, Brodie ED III and Wade MJ (eds.) (2000) Epistasis and the Evolutionary Process. Oxford: Oxford University Press.

Further Reading

Frankel WN and Schork NJ (1996) Who's afraid of epistasis? Nature Genetics 14: 371–373.

Hansen TF and Wagner GP (2001) Epistasis and the mutation load: a measurement–theoretical approach. Genetics 158: 477–485.

Jannink J‐I and Jansen R (2001) Mapping epistatic quantitative trait loci with one‐dimensional genome searches. Genetics 157: 445–454.

Tiwari HK and Elston RC (1998) Restrictions on components of variance for epistatic models. Theoretical Population Biology 54: 161–174.

Wiehe T and Slatkin M (1998) Epistatic selection in a multi‐locus Levene model and implications for linkage disequilibrium. Theoretical Population Biology 53: 75–84.

Web Links

Breast cancer 1, early onset (BRCA1); Locus ID: 672.LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=672

Caspase recruitment domain family, member 15 (CARD15); Locus ID: 64127. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=64127

Non‐insulin‐dependent diabetes mellitus (common, type 2) 1 (NIDDM1); Locus ID: 4812.LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4812

Breast cancer 1, early onset (BRCA1); MIM number:113705.OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?113705

Caspase recruitment domain family, member 15 (CARD15); MIM number: 605956.OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?605956

Non‐insulin‐dependent diabetes mellitus (common, type 2) 1 (NIDDM1); MIM number 601283.OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?601283

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Wilson, Susan R(Jan 2006) Epistasis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005414]