Is a polygenic model of schizophrenia genetics really proven?
Response to “ A joint history of the nature of genetic variation and the nature of schizophrenia ”.* Kenneth Kendler’s article on the nature of genetic variation and the nature of schizophrenia claims that theory and empirical evidence have proven the polygenic architecture of this disorder . In fact, both theory and data are entirely consistent with a very different model of high genetic heterogeneity, where the disorder is largely caused in individuals by one or a few mutations in any of a large number of genes, incorporating important and complex effects of genetic background. KK provides a scholarly overview of the history of ideas in these intertwined fields 1 . While historically interesting, the early arguments between biometricians and Mendelians about continuous versus dichotomous traits conflate two distinct questions: (i) what type of genetic variation contributes to the gradual evolution of new species?, and (ii) what type of genetic