and schizophrenia. Of seven downstream genes that are also differentially expressed between KO and wildtype, three genes (Cast, Trpm2 and Pdlim5) are associated with stress response, alcoholism and schizophrenia. Cast was identified as the susceptibility gene for alcohol dependence through genome-wide association study in humans.57 Trpm2 is highly expressed in the brain and is involved in response to stress and in the genetic etiology of bipolar disorder.58 Pdlim5 has been identified as a potential susceptibility gene for schizophrenia in humans.59 These results not only demonstrate a link between sequence differences, variation in transcript abundance and phenotypes, but also imply that Per3 is an excellent candidate gene for alcohol and stress responses.
