Study Report

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Basic Info

Reference	Kishi, T.,2011(c) PMID: 22080789
Citation	Kishi, T., R. Yoshimura, et al. (2011). "The CLOCK gene and mood disorders: a case-control study and meta-analysis." Chronobiol Int 28(9): 825-833.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	867 BP patients (621 with BP-I and 246 with BP-II), 139 MDD patients and 889 controls
SNP/Region/Marker Size	3 SNPs
Predominant Ethnicity	Mongloid
Population	Japanese
Gender	Male/female:425/442 in BD patients ,58/81 in MDD patients and 429/ 460 in controls
Age Group	Adults : Mean age(SD)(year):50.7(14.2) in BD patients ,51.4(15.5) in MDD patients and 50.0(13.5) in controls

Detail Info

Sample Diagnosis	DSM
Sample Status	All subjects were unrelated, ethnically Japanese, and residing in Japan. All MDD patients underwent a Mini-International Neuropsychiatric Interview (MINI), and all BP patients and controls were also diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria with the consensus of at least two experienced psychiatrists on the basis of unstructured interviews. None had severe medical complications, such as liver cirrhosis, renal failure, heart failure, or other Axis I disorders according to DSM-IV. The study was described to subjects and written informed consent was obtained from each (Portaluppi et al., 2010). 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 the RIKEN Brain Science Institute, Kohnodai Hospital, Teikyo University, Okayama University, and Fujita Health University) provided the BP and control samples.
Technique	genotyping
Statistical Method	We performed a logistic regression analysis to compare the frequencies of each SNP genotype for the target phenotype across patients and controls in allele, recessive, dominant, and codominant models (Zintzaras & Lau, 2008). In addition, we controlled the multiple regression analyses for age at time of recruitment and sex to adjust the results for potential confounding by these variables.Haplotype-wise association analysis was conducted with a likelihood-ratio test using the COCAPHASE2.403 program (Dudbridge, 2003).
Result Summary	We did not detect any associations between tagging SNPs in CLOCK and BP or MDD in the allele, genotype, or haplotype analysis (global p(BP)=.605 and global p(MDD)=.211). Moreover, rs1801260 was also not associated with BP, MDD, or any mood disorders in the meta-analysis. In conclusion, these data suggest that CLOCK does not play a major role in the pathophysiology of mood disorders.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 3)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs1801260	CLOCK TMEM165	T>C	For BD: Allele T, unadjusted analyses, OR=1.05, 95%CI=0.878-1.26, P-value = 0.589; adjusted analyses, OR=1.06, 95%CI=0.889-1.27, P-value = 0.498. Recessive: genotype TT and TC, unadjusted analyses, OR=1.13, 95%CI=0.662-1.94, P-value = 0.654; adjusted analyses, OR=1.16, 95%CI=0.678-1.98, P-value = 0.596 .Dominant: genotype TT, unadjusted analyses, OR=1.05, 95%CI=0.853-1.29, P-value = 0.655; adjusted analyses, OR=1.07, 95%CI=0.866-1.31, P-value = 0.546. Co-dominant: genotype TT, unadjusted analyses, OR=1.12, 95%CI=0.750-1.67, P-value = 0.582; adjusted analyses, OR=1.15, 95%CI=0.771-1.72, P-value = 0.492; Co-dominant: genotype TC, unadjusted analyses, OR=1.04, 95%CI=0.675-1.61, P-value = 0.859; adjusted analyses, OR=1.04, 95%CI=0.671-1.61, P-value = 0.871	No significant association was observed. No significant association was observed.	Negative
rs3736544	CLOCK TMEM165	G>T	For BD: Allele G, unadjusted analyses, OR=0.937, 95%CI=0.799-1.10, P-value = 0.426; adjusted analyses, OR=0.93, 95%CI=0.792-1.09, P-value = 0.37. Recessive: genotype GG and GT, unadjusted analyses, OR=0.77, 95%CI=0.500-1.17, P-value = 0.23; adjusted analyses, OR=0.762, 95%CI=0.491-1.17, P-value = 0.22 .Dominant: genotype GG, unadjusted analyses, OR=0.96, 95%CI=0.792-1.16, P-value = 0.675; adjusted analyses, OR=1, 95%CI=0.825-1.21, P-value = 0.989. Co-dominant: genotype GG, unadjusted analyses, OR=0.834, 95%CI=0.594-1.17, P-value = 0.293; adjusted analyses, OR=0.864, 95%CI=0.612-1.22, P-value = 0.404; Co-dominant: genotype GT, unadjusted analyses, OR=0.847, 95%CI=0.590-1.21, P-value = 0.365; adjusted analyses, OR=0.799, 95%CI=0.554-1.15, P-value = 0.227	No significant association was observed. No significant association was observed.	Negative
rs3749474	CLOCK TMEM165	T>C	For BD: Allele T, unadjusted analyses, OR=1, 95%CI=0.873-1.15, P-value = 0.984; adjusted analyses, OR=1.03, 95%CI=0.875-1.15, P-value = 0.968. Recessive: genotype TT and TC, unadjusted analyses, OR=0.919, 95%CI=0.704-1.20, P-value = 0.533; adjusted analyses, OR=0.954, 95%CI=0.730-1.28, P-value = 0.733 .Dominant: genotype TT, unadjusted analyses, OR=1.05, 95%CI=0.866-1.27, P-value = 0.634; adjusted analyses, OR=1.09, 95%CI=0.899-1.32, P-value = 0.379. Co-dominant: genotype TT, unadjusted analyses, OR=1.02, 95%CI=0.777-1.34, P-value = 0.883; adjusted analyses, OR=1.09, 95%CI=0.823-1.43, P-value = 0.562; Co-dominant: genotype TC, unadjusted analyses, OR=0.878, 95%CI=0.673-1.15, P-value = 0.339; adjusted analyses, OR=0.871, 95%CI=0.666-1.14, P-value = 0.312	No significant association was observed. No significant association was observed.	Negative

Genes reported by this study for BD (count: 1)

Gene	Statistical Values/Author Comments	Result Category
CLOCK	We did not detect any associations between tagging SNPs in CLOCK and BP or MDD. We did not detect any associations between tagging SNPs in CLOCK and BP or MDD.	Negative

Genetic factors reported by this study for SZ and/or MDD

SNPs reported by this study for SZ/MDD

Disease	SNP	Related Gene(s)	Statistical Values	Description	Result Category
MDD	rs1801260	CLOCK TMEM165	For MDD:Allele T, unadjusted analyses, OR=1.12, 95%CI=0.790-1.59, P-value = 0.519;adjusted analyses, OR=1.13, 95%CI=0.785-1.59, P-value = 0.542. Recessive:genotype TT and TC, unadjusted analyses, OR=1.07, 95%CI=0.359-2.57, P-value = 0.893;adjusted analyses, OR=1.08, 95%CI=0.364-2.62, P-value = 0.87 .Dominant:genotype TT, unadjusted analyses, OR=0.85, 95%CI=0.562-1.26, P-value = 0.428;adjusted analyses, OR=0.847, 95%CI=0.560-1.26, P-value = 0.422. Co-dominant:genotype TT, unadjusted analyses, OR=0.898, 95%CI=0.401-1.78, P-value = 0.761;adjusted analyses, OR=0.898, 95%CI=0.403-1.79, P-value = 0.773;Co-dominant:genotype TC, unadjusted analyses, OR=1.3, 95%CI=0.550-2.86, P-value = 0.525;adjusted analyses, OR=1.32, 95%CI=0.557-2.91, P-value = 0.504	No significant association was observed.	Negative
MDD	rs3736544	CLOCK TMEM165	For MDD:Allele G, unadjusted analyses, OR=0.783, 95%CI=0.585-1.05, P-value = 0.0989;adjusted analyses, OR=0.787, 95%CI=0.588-1.05, P-value = 0.106. Recessive:genotype GG and GT, unadjusted analyses, OR=2.19, 95%CI=1.10-4.10, P-value = 0.0187(0.224);adjusted analyses, OR=2.23, 95%CI=1.11-4.20, P-value = 0.0174(0.209) .Dominant:genotype GG, unadjusted analyses, OR=1.18, 95%CI=0.818-1.69, P-value = 0.372;adjusted analyses, OR=1.12, 95%CI=0.774-1.60, P-value = 0.551. Co-dominant:genotype GG, unadjusted analyses, OR=1.75, 95%CI=0.986-3.04, P-value = 0.0506;adjusted analyses, OR=1.67, 95%CI=0.939-2.92, P-value = 0.074;Co-dominant:genotype GT, unadjusted analyses, OR=0.161, 95%CI=0.873-2.96, P-value = 0.123;adjusted analyses, OR=1.74, 95%CI=0.940-3.21, P-value = 0.0751	Significant association was observed in recessive model , but this significance did not survive Bonferroni correction.	Positive
MDD	rs3749474	CLOCK TMEM165	For MDD:Allele T, unadjusted analyses, OR=0.938, 95%CI=0.724-1.22, P-value = 0.63;adjusted analyses, OR=0.937, 95%CI=0.723-1.22, P-value = 0.626. Recessive:genotype TT and TC, unadjusted analyses, OR=1.35, 95%CI=0.828-2.14, P-value = 0.21;adjusted analyses, OR=1.33, 95%CI=0.816-2.11, P-value = 0.233 .Dominant:genotype TT, unadjusted analyses, OR=0.958, 95%CI=0.667-1.38, P-value = 0.817;adjusted analyses, OR=0.922, 95%CI=0.641-1.34, P-value = 0.665. Co-dominant:genotype TT, unadjusted analyses, OR=1.06, 95%CI=0.609-1.77, P-value = 0.821;adjusted analyses, OR=1.01, 95%CI=0.607-1.68, P-value = 0.972;Co-dominant:genotype TC, unadjusted analyses, OR=1.4, 95%CI=0.851-2.32, P-value = 0.185;adjusted analyses, OR=1.45, 95%CI=0.874-2.40, P-value = 0.152	No significant association was observed.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
MDD	CLOCK	We did not detect any associations between tagging SNPs in CLOCK and BP or MDD	Negative