ABSTRACT
INTRODUCTION An inherited component to schizophrenia has been long established and even noted by Emil Kraepelin in his classical textbook on psychiatry (1). Since Kraepelin´s observations, extensive family, twin, and adoption studies have provided compelling evidence that schizophrenia not only tends to run in families but that this is largely due to genes. However, the mode of inheritance is clearly non-Mendelian, nor can it be, as was once thought, explained by a single gene with incomplete penetrance (i.e., where individuals who carry the gene do not necessarily express the illness). Rather, schizophrenia is best explained by a polygenic multifactorial model where many genes, each of small effect, combine with environmental factors and that the disorder results once a critical threshold of liability is exceeded. This “common disease-common alleles with multiple genes of small effect” model is the basis for large-scale genetic association and genome-wide association studies.
