Alzheimer's disease affects millions of people worldwide and incidence is expected to rise as the population ages, but no effective therapies exist despite decades of research and more than 20 known disease markers. Research has shown that Alzheimer's disease's missing heritability remains extensive with an estimated 25% of phenotypic variance unexplained by known variants. The missing heritabi...

The existence of epistasis in humans was first predicted by Bateson in 1909. Epistasis describes the non-linear, synergistic interaction of two or more genetic loci, which can substantially modify disease severity or result in entirely new phenotypes. The concept has remained controversial in human genetics because of the lack of well-characterized examples. In humans, it is only possible to de...

Consequences of directional selection on metabolic flux are explored in models for which variation in flux among individuals is generated by segregation of allelic variants at enzyme activity loci. The pattern of selection response is strongly affected by the presence of genetic dominance and epistasis, which are automatically generated in metabolic systems. The expected magnitudes of dominance...

Background Evolutionary adaptation is a process where a population increases its “fit” to the world it inhabits, and is often likened to climbing a hill or peak. While this process is trivial for fitness landscapes where each mutation provides an advantage (or disadvantage) to the organism that is independent of the fitness effect of a mutation on a different locus, the interaction between muta...

Epistasis for fitness means that the selective effect of a mutation is conditional on the genetic background in which it appears. Although epistasis is widely observed in nature, our understanding of its consequences for evolution by natural selection remains incomplete. In particular, much attention focuses only on its influence on the instantaneous rate of changes in frequency of selected all...

7 High-order epistasis has been observed in many genotype-phenotype maps. These multi-way inter8 actions could have profound implications for evolution and may be useful for dissecting complex 9 traits. Previous analyses have assumed a linear genotype-phenotype map, and then applied a linear 10 high-order epistasis model to dissect epistasis. The assumption of linearity has not been tested 11 i...

In a comment [1] on our manuscript “Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein” [2], Dr. Crona challenges our assertion that shared entropy (that is, information) between two residues implies epistasis between those residues by constructing an explicit example of three loci (say A, B, and C), in which A and B are epistatically linked ...

Epistasis and genetic variance heterogeneity are two non-additive genetic inheritance patterns that are often, but not always, related. Here we use theoretical examples and empirical results from earlier analyses of experimental data to illustrate the connection between the two. This includes an introduction to the relationship between epistatic gene action, statistical epistasis, and genetic v...

Fine, so what does a population geneticist mean by epistasis? RA Fisher used ‘epistacy’ and later ‘epistasis’ to describe genetic interactions more generally [2]. We think that population geneticists hijacked this term over a decade after its coinage just to confuse the classical geneticists. OK, what does a medical doctor mean by epistasis? A thin film on the surface of a urine specimen. Enoug...

OBJECTIVE AND METHODS This paper proposes an inegrative two-stage genome-wide search for pairwise epistasis on expression quantitative trait loci (eQTL). The traits are clustered into multi-trait complexes that account for correlations between them that may result from common epistasis effects. The search is done by first screening for epistatic regions and then using dense markers within the i...