How can genetics help understand the relationship between cognitive dysfunction and schizophrenia?

Despite the consistent finding that cognitive dysfunction is a core characteristic of schizophrenia (SCZ), little is known about the underlying pathophysiology. Recent progress in human genetics, driven by large genome-wide association studies (GWAS), has provided new data about the genetic architecture of complex human traits, including cognition and SCZ. Novel analytical tools have provided unprecedented opportunities to leverage the large amount of information from GWAS. Here we review the latest findings related to genetic architecture and risk genes of SCZ and cognitive functions, and recent findings of overlapping genetic factors. The recent GWAS of SCZ implicate over 100 risk gene loci, each with a small effect. A similar genetic architecture seems to be present in cognitive domains, suggesting that these phenotypes are highly polygenic. Further, GWAS have revealed more than 20 gene loci associated with cognitive traits, including intelligence, general cognition (g-factor), reaction time and verbal-numerical reasoning. Several gene loci have been implicated in educational attainment, a proxy measure of cognitive function. Recently, overlapping gene loci were found between education and SCZ, and between SCZ and cognitive traits, suggesting common genetic risk between SCZ and cognitive dysfunction. Mathematical modeling of GWAS of cognition and SCZ indicate that only a fraction of the heritability is identified. The evidence suggests a polygenic architecture for SCZ and cognitive functions, and a large degree of shared genetic risk. This indicates novel molecular genetic mechanisms and strengthens the notion that SCZ is more likely a part of the normal distribution and not a separate entity.