Genetic insight of schizophrenia: past and future perspectives

Schizophrenia (SCZ) has a heritability of about 80%, and the search for the genetic basis of this disease has been frustrating. Because schizophrenia has no distinguishing pathology or diagnostic criteria, it is difficult to relate gene changes to discrete physiological or biochemical changes associated with the disease. Schizophrenia fits the profile of a complex disorder in which multiple genes interact along with environmental influences to produce a range of phenotypes. There is accumulating evidence that both common genetic variants with small effects and rare genetic lesions with large effects determine risk of SCZ. As recently shown, thousands of common single nucleotide polymorphisms (SNPs), each with small effect, cumulatively could explain about 30% of the underlying genetic risk of SCZ. The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research, and all the signs are that genetic research is poised to deliver crucial insights into the nature of schizophrenia. In this review, we outline a general theoretical background of genetic mechanisms involved in SCZ.