SIRT1 gene, schizophrenia and bipolar disorder in the Japanese population: an association study

• Published in: Genes, brain and behavior Vol. 10; no. 3; pp. 257 - 263
• Main Authors: Kishi, T., Fukuo, Y., Kitajima, T., Okochi, T., Yamanouchi, Y., Kinoshita, Y., Kawashima, K., Inada, T., Kunugi, H., Kato, T., Yoshikawa, T., Ujike, H., Ozaki, N., Iwata, N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2011; John Wiley & Sons, Inc
• Subjects: Adult; Asian Continental Ancestry Group - ethnology; Asian Continental Ancestry Group - genetics; Association analysis; Bipolar disorder; Bipolar Disorder - epidemiology; Bipolar Disorder - genetics; Bipolar Disorder - physiopathology; Case-Control Studies; case–control study; Chronobiology Disorders - epidemiology; Chronobiology Disorders - genetics; Chronobiology Disorders - physiopathology; Circadian rhythm; Circadian rhythms; Comorbidity - trends; Female; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study - methods; Genotypes; Haplotypes; Humans; Japan - epidemiology; Japan - ethnology; Male; Mental disorders; Middle Aged; Population studies; Schizophrenia; Schizophrenia - ethnology; Schizophrenia - genetics; Schizophrenia - physiopathology; Single-nucleotide polymorphism; SIRT1 gene; SIRT1 protein; Sirtuin 1 - genetics; tagging SNP; Japan
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/j.1601-183X.2010.00661.x

Several lines of evidence suggest that alterations in circadian rhythms might be associated with the pathophysiology of psychiatric disorders such as schizophrenia and bipolar disorder (BP). A recent study reported that SIRT1 is a molecule that plays an important role in the circadian clock system. Therefore, to evaluate the association among the SIRT1 gene, schizophrenia and BP, we conducted a case–control study of Japanese population samples (1158 schizophrenia patients, 1008 BP patients and 2127 controls) with four tagging SNPs (rs12778366, rs2273773, rs4746720 and rs10997875) in the SIRT1 gene. Marker‐trait association analysis was used to evaluate the allele and the genotype association with the χ2 test, and haplotype association analysis was evaluated with a likelihood ratio test. 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 Pall markers = 4.89 × 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.