Study Report

Reference	Kishi, T.,2011(a) PMID: 20977650
Citation	Kishi, T., Y. Fukuo, et al. (2011). "SIRT1 gene, schizophrenia and bipolar disorder in the Japanese population: an association study." Genes Brain Behav 10(3): 257-263.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	1158 schizophrenia patients, 1008 BP patients(730 with BPI and 278 with BPII) and 2127 controls
SNP/Region/Marker Size	4 SNPs
Predominant Ethnicity	Mongloid
Population	Japanese
Gender	Male/female:495/513 in BD patients ,605/553 in SZ patients and 1026/1101 in controls
Age Group	Adults : Mean age(SD)(year):47.1(14.2) in BD patients ,42.6(17.7) in SZ patients and 45.6(15.2) in controls

Sample Diagnosis	DSM
Sample Status	All subjects were unrelated to each other, ethnically Japanese and lived in the central area of Japan. A total of 1016 schizophrenia patients and 997 BP patients were diagnosed according to DSM-IV criteria with the consensus of at least two experienced psychiatrists on the basis of unstructured interviews and a review of medical records. Of them, 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 = 407), disorganized type (n = 232), catatonic type (n = 49), residual type (n = 385) and undifferentiated type (n = 85). A total of 1950 controls were also diagnosed according to DSM-IV criteria with the consensus of at least two experienced psychiatrists on the basis of unstructured interviews, including 46 and 131 who 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. This sample panel was the same as used in the Collaborative Study of Mood Disorder consortium study. Seven laboratories (National Institute of Neuroscience, two laboratories of RIKEN Brain Science Institute, Kohnodai Hospital, Teikyo University, Okayama University and Fujita Health University) provided case and control samples. The study was described to the subjects and written informed consent was obtained from each.
Technique	genotyping
Statistical Method	Genotype deviation from the Hardy-Weinberg equilibrium (HWE) was evaluated by X2 test (SAS/Genetics, release 8.2, SAS Japan Inc,Tokyo, Japan). Marker-trait association analysis was used to evaluate allele and genotype association with the X2 test (SAS/Genetics, release 8.2, SAS Japan Inc) and haplotype association analysis was done with a likelihood ratio test using the COCAPHASE2.403 program (Dudbridge 2003).
Result Summary	We showed an association between rs4746720 in the SIRT1 gene and schizophrenia in the allele and the genotype analysis. However, the significance of these associations did not survive after Bonferroni's correction for multiple testing. On the other hand, the SIRT1 gene was associated with Japanese schizophrenia in a haplotype-wise analysis (global P(all markers) = 4.89 x 10(-15)). Also, four tagging SNPs in the SIRT1 gene were not associated with BP. In conclusion, the SIRT1 gene may play an important role in the pathophysiology of schizophrenia in the Japanese population.