Just as evolutionary theory provides a strong argument in favor of rare variants, standard quantitative genetic theory provides ample support for the infinitesimal model7,8. Whatever the causes of the maintenance of genetic variance may be, the consistent observation is that all diseases have significant heritability, and hence purifying selection has been unable to purge the population of disease-promoting variants2. At face value, the existence of dozens of susceptibility alleles for metabolic and immunological diseases with effect sizes that are just not detected for psychological diseases implies a difference in genetic architecture between the two categories of conditions. This may imply different intensities of purifying selection, although other models, including decanalization69, are also compatible with the data. Since the majority of the genetic variance remains unexplained, it is a priori just as likely to exist in the form of rare or common alleles, and the fact is that there is nothing about GWAS findings that is inconsistent with the infinitesimal model of many variants of very small effect across the full allele frequency spectrum. This model has served applied quantitative geneticists
