Study Report

Reference	Kishi, T.,2011(b) PMID: 20594600
Citation	Kishi, T., T. Okochi, et al. (2011). "Serotonin 1A receptor gene, schizophrenia and bipolar disorder: an association study and meta-analysis." Psychiatry Res 185(1-2): 20-26.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	857 schizophrenic patients, 1028 BP patients and 1810 controls
SNP/Region/Marker Size	3 SNPs
Predominant Ethnicity	Mongloid
Population	Japanese

Sample Diagnosis	DSM
Sample Status	715 schizophrenic patients and 1017 BP patients were diagnosed according to Diagnostic and Statistical Manual for Mental Disorders (DSM)-IV criteria with the consensus of at least two experienced psychiatrists on the basis of unstructured interviews and a review of medical records. As many as 142 schizophrenic patients and 11 BP patients underwent the Structured Clinical Interview for DSM-IV disorders (SCID-1). Schizophrenic patients were grouped according to the following DSM-IV subtypes of schizophrenia: paranoid type (n=221), disorganised type (n=224), Catatonic type (n=29), residual type (n=143) and undifferentiated type (n=125). A total of 1633 controls were also diagnosed according to DSM-IV criteria with the consensus of at least two experienced psychiatrists on the basis of unstructured interviews, of which 46 and 131 controls underwent the Mini-International Neuropsychiatric Interview (MINI) and SCID-1, respectively. None had severe medical complications such as liver cirrhosis, renal failure, heart failure or other Axis-I disorders according to DSM-IV. Controls included hospital staff and medical students. Our control samples may not be representative of the general population.
Technique	genotyping
Statistical Method	Marker-trait association analysis was used to evaluate allele- and genotype-wise association with the chi-square test (SAS/Genetics, release 8.2, SAS Japan Inc., Tokyo, Japan). The distribution of patient characteristics in the schizophrenia group, BP group and healthy control group was analysed using a t test or a chi-square test.A haplotype-wise association analysis was done with a likelihood ratio test using the COCAPHASE2.403 program (Dudbridge, 2003).
Result Summary	Two association studies for schizophrenia and three association studies for BP, including this study, met our criteria for the meta-analysis of rs6295. We found an association between HTR1A and Japanese BP in a haplotype-wise analysis, the significance of which remained after Bonferroni correction. In addition, we detected an association between rs6295 and BP in the meta-analysis (fixed model: P(Z)=0.000400). However, we did not detect an association between HTR1A and schizophrenia in the allele/genotype-wise, haplotype-wise or meta-analysis. HTR1A may play an important role in the pathophysiology of BP, but not schizophrenia in the Japanese population. In the meta-analysis, rs6295 in HTR1A was associated with BP patients.