Genetics: Gene-Environment Interaction

Fundamentally, the science of genetics is concerned with the explanation of differences among organisms. Some theories and methods pertain to the differences among species; others concern the individual differences among members of the same species—the subject matter of this section.

Historically, Mendelian genetics was categorical, dealing with individual differences that could be characterized by assignment of individuals to one or another of two or three categories. Analytic logic compared the observed categorical status of individuals to expectations (hypotheses) derived from Mendel's theory. As long as category assignment was unambiguous, it was a matter of small concern that there might exist individual differences within categories, derived presumably from environmental sources or from genes other than the one under examination. Enormous advances in understanding the basics of inheritance were made from the comfortably simple logical stance of "all and only" causal analysis—all cases of a particular genotype (genetic constitution) were accompanied by the particular phenotype (a measured or observed attribute), and all cases of the phenotype occurred in the presence of that genotype. There were some puzzling exceptions, however. Sometimes, individuals who almost certainly had a particular genotype did not display the associated phenotype. Furthermore, it was observed that the actual manifestation of the phenotype could vary greatly among individuals with the same genotype (with respect to the relevant single locus). Explanations were sought for these cases of reduced penetrance or variable expressivity both in terms of the effects of "modifier" genes or of environmental influence on the phenotype.

The biometrical approach to inheritance concerned phenotypic domains that were not dior trichotomous but were instead continuously distributed. Individuality was measured as variance rather than as categorical membership and the logic underlying analysis concerned the degree of phenotypic similarity of individuals of differing degrees of biological relatedness. Initially thought to concern a fundamentally different type of inheritance from the Mendelian, it was shown early in the twentieth century that the basic difference was in the effect size of the relevant genetic factors. Quantitative or continuously distributed phenotypes were theorized to be due to the collective influence of many genes (polygenic inheritance), each of which acted according to Mendelian rules but with individually small effects. The statistical model of quantitative genetics identifies both genetic and environmental sources of individuality, and partitions the variability among individuals into components attributable to these domains. The model also necessarily acknowledges, by means of interaction and covariance terms, the possibilities of interrelationships of factors from these domains.

Thus, with respect both to classical genes of major categorical effect and the polygenes of quantitatively distributed phenotypes, the possibility that the influences of genes are importantly conditioned by environmental context must be considered. This section will provide examples of the interconnectedness of genetic and environmental effects with particular reference to age and aging, including both classical statistical interaction and reciprocal influence between the genetic and environmental domains. It is not intended to be an exhaustive review, but merely to be illustrative of the types of interaction and co-action that can be expected as research on genetic influence on aging processes advances.