Association study of clock gene (CLOCK) and schizophrenia and mood disorders in the Japanese population

Kishi, Taro; Kitajima, Tsuyoshi; Ikeda, Masashi; Yamanouchi, Yoshio; Kinoshita, Yoko; Kawashima, Koichiro; Okochi, Tomo; Okumura, Takenori; Tsunoka, Tomoko; Inada, Toshiya; Ozaki, Norio; Iwata, Nakao

doi:10.1007/s00406-009-0869-4

Cited by 79 publications

(59 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Far less is known regarding the involvement of circadian genes in the vulnerability to MDD. No evidence of association was found between a CLOCK gene variation in MDD (Bailer et al, 2005;Desan et al, 2000;Kishi et al, 2009a), although a positive association with fluvoxamine response was reported in Japanese MDD patients (Kishi et al, 2009b).…”

Section: Introductionmentioning

confidence: 86%

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Soria

Martínez‐Amorós

Escaramís

et al. 2010

Neuropsychopharmacol

315

203

View full text Add to dashboard Cite

Disruptions in circadian rhythms have been described in mood disorders (MD), but the involvement of genetic variation in genes pertaining to the molecular circadian machinery in the susceptibility to MD has not been conclusively determined. We examined 209 single-nucleotide polymorphisms (SNPs) covering 19 circadian genes (ADCYAP1, ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1E, DBP, NPAS2, NR1D1, PER1, PER2, PER3, RORA, TIMELESS, VIP, and VIPR2) in a sample of 534 MD patients (335 with unipolar major mood depression (MDD) and 199 with bipolar disorder (BD)) and 440 community-based screened controls. Nominally, statistically significant associations were found in 15 circadian genes. The gene-wide test, corrected for the number of SNPs analyzed in each gene, identified significant associations in CRY1 (rs2287161), NPAS2 (rs11123857), and VIPR2 (rs885861) genes with the combined MD sample. In the MDD subsample, the same SNPs in CRY1 and NPAS2 of the combined sample remained associated, whereas in the BD subsample CLOCK (rs10462028) and VIP (rs17083008) were specifically associated. The association with an SNP located 3 0 near CRY1 gene in MDD remained statistically significant after permutation correction at experiment level (p ¼ 0.007). Significant additive effects were found between the SNPs that were statistically significant at the gene-wide level. We also found evidence of associations between two-marker haplotypes in CRY1 and NPAS2 genes and MD. Our data support the contribution of the circadian system to the genetic susceptibility to MD and suggest that different circadian genes may have specific effects on MD polarity.

show abstract

Section: Introductionmentioning

confidence: 86%

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Soria

Martínez‐Amorós

Escaramís

et al. 2010

Neuropsychopharmacol

315

203

View full text Add to dashboard Cite

show abstract

“…Also, our control subjects did not undergo structured interviews. There may also have been a problem of sampling bias with mood disorders; for example, some patients diagnosed with MDD may develop BP in the future [45][46][47] . Second, in this study, we did not apply the 'gene-wide' approach recommended by Ikeda et al [48] to consider population differences.…”

Section: Discussionmentioning

confidence: 99%

“…The subjects in the association analysis were 325 MDD patients (160 males and 165 females; mean age 8 standard deviation 47 were treated with fluvoxamine and diagnosed according to DSM-IV criteria with the consensus of at least two experienced psychiatrists on the basis of a review of medical records and assessments with the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-D). The MDD patients other than these 117 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.…”

Section: Subjectsmentioning

confidence: 99%

Genetic Association Analysis of Functional Polymorphisms in Neuronal Nitric Oxide Synthase 1 Gene <i>(NOS1)</i> and Mood Disorders and Fluvoxamine Response in Major Depressive Disorder in the Japanese Population

et al. 2009

Self Cite

View full text Add to dashboard Cite

Background/Aim: Nitric oxide has been reported to play a role in neural transmitter release and N-methyl-D-aspartate receptor activation, as well as to be related to oxidative stress. Abnormalities in both of these mechanisms are thought to be involved in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BP). In addition, several lines of evidence support an association between abnormalities in neuronal nitric oxide synthases (nNOS) and mood disorders. Therefore, we studied the association of nNOS gene (NOS1) and mood disorders and the efficacy of fluvoxamine treatment in Japanese MDD patients. Materials and Methods: Using a single nucleotide polymorphism (SNP; rs41279104, also called ex1c), we conducted a genetic association analysis of case-control samples (325 MDD patients, 154 BP patients and 807 controls) in the Japanese population. In addition, we performed an association analysis between NOS1 and the efficacy of fluvoxamine treatment in 117 MDD patients. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D (Structured Interview Guide for the Hamilton Rating Scale for Depression) score within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Results: We did not detect a significant association between NOS1 and MDD, BP or the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis. Conclusions: We did not detect an association between only one marker (rs41279104) in NOS1 and Japanese mood disorder patients and fluvoxamine response, but sample sizes were probably too small to allow a meaningful test. Moreover, because we did not perform an association analysis based on linkage disequilibrium and a mutation scan of NOS1, a replication of the study using a larger sample and based on linkage disequilibrium may be required for conclusive results.

show abstract

“…Detailed information on our samples was provided in previous papers. [32][33][34][35] In conclusion, our results suggest that HTR1A may not have a role in the pathophysiology of Japanese MDD patients. On the other hand, according to the meta-analysis, HTR1A was associated with MDD patients, especially in the Asian population.…”

Section: Discussionmentioning

confidence: 58%

Serotonin 1A receptor gene and major depressive disorder: an association study and meta-analysis

et al. 2009

Self Cite

View full text Add to dashboard Cite

Several genetic studies have shown an association between the 5-HT1A receptor gene (HTR1A) and major depressive disorder (MDD); however, results have been rather inconsistent. Moreover, to our knowledge, no association study on HTR1A and MDD in the Japanese population has been reported. Therefore, to evaluate the association between HTR1A and MDD, we conducted a case-control study of Japanese population samples with two single-nucleotide polymorphisms (SNPs), including rs6295 (C-1019G) in HTR1A. In addition, we conducted a meta-analysis of rs6295, which has been examined in other papers. Using one functional SNP (rs6295) and one tagging SNP (rs878567) selected with the HapMap database, we conducted a genetic association analysis of case-control samples (331 patients with MDD and 804 controls) in the Japanese population. Seven population-based association studies, including this study, met our criteria for the meta-analysis of rs6295. We found an association between rs878567 and Japanese MDD patients in the allele-wise analysis, but the significance of this association did not remain after Bonferroni's correction. We also did not detect any association between HTR1A and MDD in the allele/ genotype-wise or haplotype-wise analysis. On the other hand, we detected an association between rs6295 and MDD in the metaanalysis (P(Z)¼0.0327). In an explorative analysis, rs6295 was associated with Asian MDD patients after correction for multiple testing (P(Z)¼0.0176), but not with Caucasian MDD patients (P(Z)¼0.138). Our results suggest that HTR1A may not have a role in the pathophysiology of Japanese MDD patients. On the other hand, according to the meta-analysis, HTR1A was associated with MDD patients, especially in the Asian population. Keywords: case-control study; functional SNP; major depressive disorder (MDD); meta-analysis; serotonin 1A receptor gene (HTR1A); tagging SNP INTRODUCTION Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for major depressive disorder (MDD). The evidence for such an association is discussed in more detail in reviews. 1,2 Several genetic studies have shown an association between the serotonin 1A (5-HT1A) receptor gene (HTR1A) and MDD; however, results have been rather inconsistent. A recent meta-analysis showed no association between HTR1A and MDD. 3 However, two very recent studies reported that rs6295 (C-1019G) in the promoter region of HTR1A, which regulates HTR1A transcription, 4,5 was associated with MDD in the Chinese population. 6,7 Moreover, to our knowledge, no association study of HTR1A and MDD in the Japanese population has been reported. Therefore, we examined the association between HTR1A and MDD in the Japanese, using the recently recommended strategy of 'genebased' association analysis. 8 Moreover, we conducted an updated

show abstract

Association study of clock gene (CLOCK) and schizophrenia and mood disorders in the Japanese population

Cited by 79 publications

References 40 publications

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Genetic Association Analysis of Functional Polymorphisms in Neuronal Nitric Oxide Synthase 1 Gene <i>(NOS1)</i> and Mood Disorders and Fluvoxamine Response in Major Depressive Disorder in the Japanese Population

Serotonin 1A receptor gene and major depressive disorder: an association study and meta-analysis

Contact Info

Product

Resources

About