“The paper shows that a gene’s connection to a disease can be hidden or revealed, depending on the subjects’ exposure to an environmental pathogen”

Over the past two years, we have provided the first evidence for interactions between specific genes and environments in the behavioral sciences (Caspi et al., 2002; 2003, both appearing in Science). Such GxE interactions are familiar in agriculture, but they are newer in medical research into human disease, and particularly new in psychiatry and neuroscience. Our findings provide proof of principle that (a) some susceptibility genes influence the brain’s response to environmental pathogens, and (b) the effects of certain genes on psychiatric disorders may be stronger than heretofore known, within environmentally vulnerable groups of people.

Our work demonstrates a methodology for gene hunters racing to find genes for disease. The paper shows that a gene’s connection to a disease can be hidden or revealed, depending on the subjects’ exposure to an environmental pathogen. In such interactions, the gene-disease connection will be diluted in un-exposed subjects, concealing potentially strong gene-disease connections. Therefore, if exposure to environmental pathogens is not measured, candidate genes will appear to have small or nil associations with disease, and genome-wide scans may overlook genes connected with disease, even in the largest samples. Our research recommends the following: to find genes for diseases with known environmental causes, ascertain environmental exposure, and use it as a magnifying research tool to reveal the connection between gene and disease outcome.

We noticed that reports of connections between genes and diseases often failed to replicate, and we wondered if that failure was because the connection was conditional on some unmeasured, unobserved factor that contributed to disease causation.

For diseases that are common in the population, and that already have known non-genetic environmental causes, a person’s risk of developing the disease can depend on whether a genetic susceptibility in their family is met with the environmental cause. These are diseases such as depression and heart disease, in which a family genetic susceptibility might not result in disease unless the person suffers stress, or eats a high-fat diet.