Understanding the genetic architectonics of complex CNS traits: Lost by the association, but found in the interaction?

Abstract

Recent evidence supports the value of endophenotypes and genome-wide association studies in psychiatric genetics, and their importance for dissecting the neural pathways and molecular mechanisms of complex neuropsychiatric disorders. Continuing this important discussion, here we outline three new mechanisms by which novel classes of genes may facilitate CNS pathogenesis without directly worsening its individual 'established' endophenotypes. These putative genetic mechanisms can apply to other human disorders in general, and may also be used for designing novel effective CNS drug treatments.

Keywords: Brain disorder; endophenotype; neuropsychiatric domain; pathogenetic interplay/overlap; spectrum of brain disorders.