Gene and Environment

There are many potential patterns of interaction that could exist between genetic and environmental factors for a phenotype. Several plausible statistical models of gene-environment interaction have been described. Phenotype expression can either be:

1. Increased only in the presence of both the susceptibility genotype and the environmental factor;
2. Increased by the environmental factor alone but not by the genotype alone;
3. Increased by the genotype alone but not by the environmental factor alone;
4. Increased by either, with joint effects being additive or multiplicative;
5. Reduced by the genotype and not affected by the environmental factor alone, but increased in the presence of both; or
6. Reduced by the genotype, increased by the environmental factor, and increased by the presence of both.

These models are simple and consider the effect of only one gene and one environmental factor. Interactions are likely to be much more complex, involving multiple genes, multiple environmental factors, genetic heterogeneity, and heterogeneity of exposure. However, finding statistical interaction between two factors is just the first step in unraveling a complex phenotype. Once statistical interactions are identified, other laboratory studies may be performed to establish what biological interactions, if any, exist.

The level of cholesterol in the bloodstream is an example of a trait that is caused by a complex set of genetic and environmental factors. In families with familial hypercholesterolemia (FHC), elevated cholesterol levels are inherited in a Mendelian, autosomal dominant pattern. However, only about 4 percent of all individuals in the top 5 percent of cholesterol levels in the population carry the gene responsible for FHC. Other genetic and environmental risk factors clearly influence cholesterol levels. For example, in people with and without FHC, consumption of cholesterol in the diet independently modifies cholesterol levels. Other factors such as exercise and medication use likely interact with dietary intake to determine blood levels of cholesterol. Other genetic factors may also be involved.

With the exception of a relatively small number of phenotypes that are completely genetically determined, almost all human phenotypes represent a combination of environmental and genetic factors. Understanding the ways in which genes and environment work together to impact human health is one of the great challenges in the study of complex phenotypes.