The relationship between genotype and phenotype is influenced by the complex and dynamic interplay of both genetic and environmental factors. While a variety of statistical methodologies capable of detecting gene-by-gene (GxG) and gene-by environment (GxE) interactions at the population level have been developed, an axiomatic mathematical framework capable of seamlessly describing the effects of genetic alterations and environmental exposures on a common scale is lacking. Using buffering concepts, Dr. Karagiannis aims to develop a universally applicable paradigm for genetic analysis that is capable of quantitatively communicating the phenotypic effects of individual alleles and their interactions with both genetic and environmental factors.