CRY1 Variations Impacts on the Depressive Relapse Rate in a Sample of Bipolar Patients.

Drago A, Monti B, De Ronchi D, Serretti A. Psychiatry Investig. 2015 Jan;12(1):118-24.

The purpose of this paper was to investigate the mediatory effects of polymorphisms in the cry1 gene on depressive and manic relapses in those with bipolar disorder (based on DSM-IV criteria). The study of 654 American bipolar patients has found a SNP in cry1 (rs10861688) that is associated with the number of depressive events in bipolar disorder.

rs10861688 in cry1

cry1 rs10861688

NCBI Variation Viewer rs10861688


SIRT1 gene is associated with major depressive disorder in the Japanese population.

Kishi T, Yoshimura R, Kitajima T, Okochi T, Okumura T, Tsunoka T, Yamanouchi Y, Kinoshita Y, Kawashima K, Fukuo Y, Naitoh H, Umene-Nakano W, Inada T, Nakamura J, Ozaki N, Iwata N. J Affect Disord. 2010 Oct;126(1-2):167-73.

Given the many studies of circadian genes and mood disorders, the authors investigated sirt1 SNPs as mediators of the pathogenesis of Hamilton Rating Scale for Depression diagnosed major depressive disorder (MDD). The study of 450 Japanese people with MDD and 766 healthy controls working in hospitals found that a sirt1 gene SNP (rs10997875) is associated with MDD. The authors also tested for a gene-anti-depressant interaction, but the association was not significant.

rs10997875 in sirt1

sirt1 rs10997875

NCBI Variation Viewer rs10997875

The association of CLOCK gene T3111C polymorphism and hPER3 gene 54-nucleotide repeat polymorphism with Chinese Han people schizophrenics.

Zhang J, Liao G, Liu C, Sun L, Liu Y, Wang Y, Jiang Z, Wang Z. Mol Biol Rep. 2011 Jan;38(1):349-54.

To explain the altered sleep patterns in people with schizophrenia, a Chinese study of 148 schizophrenics (as diagnosed via Chinese classification and diagnostic criteria of mental disorders-2nd Edition-Revised) and 199 controls assessed the associations between the clock SNP rs1801260 and schizophrenia.

The study found that those with schizophrenia (as diagnosed by the Chinese classification and diagnostic criteria of mental disorders-2nd Edition-Revised) were more likely to have this SNP.

rs1801260 in clock

Clock rs1801260

NCBI Variation Viewer rs1801260

A polymorphism at the 3′-untranslated region of the CLOCK gene is associated with adult attention-deficit hyperactivity disorder.

Kissling C, Retz W, Wiemann S, Coogan AN, Clement RM, Hünnerkopf R, Conner AC, Freitag CM, Rösler M, Thome J. Am J Med Genet B Neuropsychiatr Genet. 2008 Apr 5;147(3):333-8.

The purpose of this study was to assess the relationship between SNPs in the clock gene and adult attention-deficit hyperactivity disorder (ADHD). The study included 143 German men aged 31.3 ± 11.7 (mean ± standard deviation), who were genotyped for SNPs via blood samples and ADHD status was assessed by self report followed by the WenderReimherr diagnostic interview.

A SNP in the clock gene (rs1801260) was found to be associated with ADHD by non-parametric analysis of covariance, adjusting for age, presence of personality disorders and multiple comparisons. Compared to those homozygous for the C/C alleles, those homozygous for the T/T allele had higher scores on measures of ADHD.

rs1801260 in clock

Clock rs1801260

NCBI Variation Viewer rs1801260

Genetic variation in circadian rhythm genes CLOCK and ARNTL as risk factor for male infertility.

Hodžić A, Ristanović M, Zorn B, Tulić C, Maver A, Novaković I, Peterlin B. PLoS One. 2013;8(3):e59220.

A case-control study was performed to determine the role of circadian genes in male infertility. The study consisted of 517 cases and 444 controls, all of which were of Slavic origin and recruited from three outpatient fertility centres. A chi-square test found three SNPs (rs11932595, rs6811520, and rs6850524) on the clock gene that are associated with male clinician-diagnosed infertility. A haplotype analysis was then performed and confirmed the association.

The SNPs in the clock gene

clock rs11932595, rs6811520, and rs6850524

NCBI Variation Viewer rs11932595-rs6811520-rs6850524

Polymorphism in the PER3 promoter associates with diurnal preference and delayed sleep phase disorder.

Archer SN, Carpen JD, Gibson M, Lim GH, Johnston JD, Skene DJ, von Schantz M. Sleep. 2010 May 3;(5):695-701.

This study investigated the circadian genetic influence on sleep disorders and chronotypes. Visitors to the London Science Museum were recruited and completed the Horne-Östberg diurnal preference questionnaire and provided buccal DNA samples. In addition, a second patient population of individuals diagnosed with delayed sleep phase disorder (DSPD) were investigated. The authors found that those with the rs2797687 SNP on per3 were more likely to have DSPD compared to individuals with an evening chronotype. The TA2G haplotype was also associated with DSPD, as compared to evening chronotypes.

rs2797687 SNP in per3

per3 rs2797687

NCBI Variation Viewer rs2797687

ARNTL (BMAL1) and NPAS2 gene variants contribute to fertility and seasonality

Kovanen L, Saarikoski ST, Aromaa A, Lönnqvist J, Partonen T. PLoS One. 2010; 5(4): e10007.

This Finnish study aimed to investigate the relationship between circadian clock genes and fertility. 511 subjects, aged 30 or older, were recruited from a national cohort. They underwent a diagnostic mental health interview, completed a modified Seasonal Pattern Assessment Questionnaire and genotyping was performed from patient blood samples.

Many nominally significant associations were found before correcting for multiple testing. The one association still significant after false discovery rate adjustment was that women homozygous for the rs2278749 SNP in the bmal1 gene experience a higher number of miscarriages than those with a wild type allele.

rs2278749 in bmal1

bmal1 rs2278749

NCBI Variation Viewer rs2278749

CRY1 circadian gene variant interacts with carbohydrate intake for insulin resistance in two independent populations: Mediterranean and North American.

Dashti HS, Smith CE, Lee YC, Parnell LD, Lai CQ, Arnett DK, Ordovás JM, Garaulet M. Chronobiol Int. 2014 Jun;31(5):660-7.

A study in 820 North Americans and 728 people living in the Mediterranean area was carried out to evaluate the role of genetics in insulin resistance. The subjects were recruited from weight loss clinics (Mediterranean) or from the Blood Institute Family Heart Study field centers (American), and measures of blood and diet via (Diet History Questionnaire or 24 hour recall) were recorded.

The author found that greater carbohydrate intake is associated with increased insulin resistance in Mediterraneans with the CC allele of cry1 SNP rs2287161 versus those with non-CC alleles. This effect was nearly significant in the North American population as well. Additionally, they found that the effect of carbohydrate intake on predicted insulin resistance was dependant on genotype.

rs2287161 in cry1

cry1 rs2287161

NCBI Variation Viewer rs2287161

Association of Tef polymorphism with depression in Parkinson disease.

Hua P, Liu W, Kuo SH, Zhao Y, Chen L, Zhang N, Wang C, Guo S, Wang L, Xiao H, Kwan JY, Wu T. Mov Disord. 2012 Nov;27(13):1694-7.

Parkinson’s disease patients tend to develop depression, and the authors of this paper assessed the role of circadian genetics in its pathogenesis. A genetic association study was performed in 408 Chinese patients with Parkinson’s Disease, and after adjusting for demographics, disease severity and treatment dose, the study found that the tef  SNP rs738499 is associated with symptoms of depression (via the Hamilton Rating Scale for Depression) in people with Parkinson’s Disease.

rs738499 in tef

tef rs738499

NCBI Variation Viewer rs738499

PER2 rs2304672 Polymorphism Moderates Circadian-Relevant Reward Circuitry Activity in Adolescents

Forbes EE, Dahl RE, Almeida JR, Ferrell RE, Nimgaonkar VL, Mansour H, Sciarrillo SR, Holm SM, Rodriguez EE, and Phillips ML. Biol Psychiatry. 2012 Mar 1;71(5):451-7.

The purpose of this study of 90 adolescents was to determine the relationship between SNPs in circadian genes and reward mediating brain circuitry. The authors found that carriers of the G allele for the rs2304672 SNP in per2 tended to have less brain activity in the medial prefrontal cortex, an area of the brain associated with self-regulation, as measured by functional magnetic resonance imaging (fMRI).

rs2304672 in per2

per2 rs2304672
NCBI Variation Viewer rs2304672