PICK1 is not a susceptibility gene for schizophrenia in a Japanese population: association study in a large case-control population.

The protein interacting with C-kinase 1 (PICK1) has been implicated in the susceptibility to schizophrenia. PICK1 interacts with enzymes and receptors that play roles in the pathogenesis of schizophrenia via glutamatergic dysfunction. Recently, two studies reported associations between schizophrenia and two PICK1 gene polymorphisms, rs3952 in Chinese and Japanese populations and rs2076369 in a Japanese population. We attempted to confirm these associations in a case-control study of 1765 Japanese patients with schizophrenia and 1851 Japanese control subjects. Neither polymorphism was associated with schizophrenia (rs3952, p=0.755; rs2076369, p=0.997). A haplotype block with these polymorphisms spanning the 5' region of the PICK1 gene showed high linkage disequilibrium in the Japanese population (D'=0.98, r(2)=0.34); however, neither haplotype was significantly associated with schizophrenia. We conclude that the common haplotypes and polymorphisms of the PICK1 gene identified thus far are unlikely to contribute to genetic susceptibility to schizophrenia in the Japanese population.