Evolutionary genetics of affective disorders

I review evolutionary-genetic models for the generation, maintenance and loss of allelic variation underlying polygenic disease, in the context of affective disorders and related conditions. Genetically-based liability to these disorders appears to be due to some combination of mutation-selection balance involving common, small-effect variants and rare, large-effect variants, and natural selection involving antagonistic pleiotropy and balancing selection. At present, the primary usefulness of evolutionary genetics in the study of affective disorders is that it provides important insights into choices of genes, alleles, and haplotypes for analysis via genome-scan and association studies, and motivates a focus on the potential for pleiotropic, beneficial effects of alleles and genotypes that also influence disease risk.