In search of schizophrenia genes

The pathogenesis of schizophrenia involves the interaction of many genes and environmental factors. In an effort to find potential genetic risk factors for schizophrenia, research groups have published over 1200 genetic association studies with inconsistent results. Also GWAS have been published, and new genes have been identified, although replication studies are necessary. To facilitate the interpretation of these findings, the on-line "SzGene" database systematically updated all published genetic studies in schizophrenia. A meta-analysis of association studies showed significant effects in 16 genes (APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GABRB2B, HP, IL1B, MTHFR, PLXNA2, SCLC6A4, TP53 and TPH1). The elucidation of the genotype-phenotype relationship is at an early stage, but current findings highlight the need to consider alternative approaches to classification for psychiatric genetic research. Our understanding of brain mechanisms that link specific gene actions and products to the subjective experience of psychopathological symptoms is likely to be bridged by employing intermediate phenotypes in domains such as cognition, neuropsychology and neuroanatomy.