Introduction: Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To\r\novercome this state of uncertainty, the SZGene database has been established by including all published casecontrol\r\ngenetic association studies appearing in peer-reviewed journals. In the current study, we aimed to\r\ndetermine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our casecontrol\r\nsamples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of\r\nseven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative\r\ndiagnostic manual, the DSM-IV.\r\nMethods: Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven\r\ntop-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February,\r\n2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the\r\ndisorder based on the participantsââ?¬â?¢ genetic information, we calculated the ââ?¬Å?risk-indexââ?¬Â by adding the number of\r\ngenetic risk factors.\r\nResults: No statistically significant deviation between cases and controls was observed in the genetic risk-index\r\nderived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the\r\nschizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39).\r\nConclusion: The current work illustrates the difficulty in identifying universal and definitive risk-conferring\r\npolymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the\r\npossibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is\r\nalso important to aggregate the updated positive variants in the SZGene database when the replication work is\r\nconducted.
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