Interestingly, a three-way interaction of genetic variations, DNA methylation and environmental exposure was first demonstrated by Salam et al. [ 25], who showed that exposure to particulate matter and methylation levels of the NOS2 promoter haplotypes jointly influenced levels of exhaled nitric oxide.
The vitamin D receptor gene (VDR) was selected, and the interactions of genetic variation in VDR with circulating vitamin D levels and gemcitabine treatment were evaluated.
Additional work has been done on candidate genes, i.e., genes chosen a priori and not through a genome scanning studies, including several studies of CNTNAP2 and some recent work implicating BDNF as a gene x gene interaction partner of genetic variation on chromosome 13 that influences language.
It is possible that the interaction effects of genetic variation and stress on depression are moderated by gender, perhaps due to the influence of gender differences in hormone levels on gene expression, serotonergic function, and neural development.
Moreover, it is likely that interactions of genetic variations with environmental factors are required to trigger major mood disorders.
The customary partitioning involves: 1) Differences among environments in the ranking of genotypes (RC interaction) 2) Variation among environments in the expression of genetic variation (LoE interaction) .
Clearly these genotype by genotype interactions will permit the maintenance of genetic variation for characters under selection as can genotype by environment interactions.
Future work will be required to better understand the role of genotype × environment interactions in controlling the measurement of genetic variation in transcript accumulation.
In this case, ejaculate × ejaculate interactions would explain variance in the outcome of sperm competition, but it is less clear that these interactions contributed towards the maintenance of genetic variation in sperm competitive ability.
