Genetic Insights

Identifying the genetic causality of schizophrenia has become a major focus in CNS research. Multiple family, twin, and adoption studies have demonstrated that schizophrenia may be inherited. If a first-degree relative has schizophrenia there is a 10% chance of an individual developing schizophrenia, and if the first-degree relative is an identical twin the probability of developing schizophrenia rises to between 40% and 65%. However, no single specific genetic defect has yet been identified that explains this association nor has any genetic alteration been found that can account for more than a small proportion of the risk of inheriting schizophrenia. Thus schizophrenia is thought to be genetically heterogeneous with several discrete genes contributing to disease causality - the schizophrenia spectrum.24 Twin studies have also indicated that there is a major epigenetic component of schizophrenia causality,7'8 leading to the use of genome-wide scans to identify susceptibility loci.25

A large number of vulnerability genes have been identified that number in excess of 30.26'27 Many of these genetic associations have failed to replicate when examined in different patient populations while allelic variations (e.g., Val108/158Met) in other genes, e.g., catechol O-methyltransferase (COMT) have been implicated in more than one disease state, in this instance gender-related pain sensitivity, temporomandibular joint disorder, breast cancer, and blood pressure.

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