The interactions involving one SNP in an ADH and one in an ALDH gene are of biological interest since it is the combination of the relative rates at which these enzymes act which determines the amount of acetaldehyde present in an individual’s system for a given alcohol intake level. Because a genetically determined difference in the rate of one stage in the pathway could theoretically be masked by a variation at the other stage, modeling an interaction term may be the only way to uncover genetic effects. Although variants in genes acting in the same stage of alcohol metabolism may be expected to have a simple additive effect, the potential still exists for the effect of one variant to mask the effect of another. Alternatively, multiple variants may interact to put an individual’s ethanol metabolizing capacity above or below a certain threshold to make the effects detectable.
