The analytic strategies described below are based on postulates that common disease/common allele models hold for many of the variants that alter vulnerabilities to addiction and related phenotypes. Rare variants may also explain significant fractions of the genetic risk for common diseases. However, increasing evidence supports roles in addiction vulnerability for allelic variants that are currently common and are thus likely to be “old” in an evolutionary sense. Data indicating that such variants can be identified in diseased individuals from European, African and Asian genetic backgrounds also point, in general, to variants of substantial age. How could genetic selection act on such common functional allelic variants over the large number of generations that are implied by this “substantial age”? It is conceivable that some currently-common allelic variants could exert polygenic influences on addiction vulnerability without exerting positive or negative selective effects during lengthy evolutionary histories. However, it also seems likely that many allelic variants that influence addiction vulnerability can provide balancing selection; favorable in some individuals or organs or circumstances and unfavorable in other individuals or organs or circumstances. Balancing selection might thus maintain relatively high frequencies of multiple functional allelic variants in the population over long periods of time.
