Genetic epidemiology of mental disorders: Challenges in identifying genetic and environmental factors for schizophrenia

Abstract

Family studies of schizophrenia have shown that it aggregates in pedigrees, with greatest risk to the first-degree relatives of affected individuals; however, second-degree relatives are also at heightened risk relative to the general population where the risk is about 1%. ?Twin and adoption studies have established that this familial aggregation is due in part to genes, with heritability estimated at between 60 and 85% However, the less-than-absolute heritability estimate demonstrates that environmental factors and gene-environment interactions are also influential. Most families affected by schizophrenia do not show simple Mendelian inheritance patterns; instead, the transmission seems to be more complex and multifactorial, involving hundreds or even thousands of genetic and environmental risk factors, none of which is either necessary nor sufficient to cause the illness. This body of behavioral genomic research will be discussed and integrated within the context of a developmental model of schizophrenia, which passes from a risk state (schizotaxia) through an early pre-morbid state (prodrome) to full disorder and chronic illness via the interaction of risk genes and environmental factors.