How does this discussion of common disease/common allele hypotheses relate to the postulates of genetic heterogeneity noted above? None of the above discussion about common alleles and common variants precludes (or even reduces the likelihood of) contributions of rarer (or even “private”) allelic variants, including those that have arisen more recently in evolutionary time. Recently-arising variations would be much more likely to persist for a number of generations even in the face of even moderately-negative influences on survival or fertility. Indeed, based on experience with other genetic disorders, it may be worthwhile to actively search for effects of rarer “phenocopy” variants in genes that are initially identified based on common (and evolutionarily older) allelic variants [99]. A rarer copy number variant might contribute to addiction vulnerability by altering levels of expression of a gene that also contains more common allelic variants that alter expression via SNPs in other gene elements, for example [94–97]. Such considerations support searches within identified loci for molecular genetic heterogeneity relevant to addiction.
