Dataset Information

Genetic Association of the PERIOD3 (Per3) Clock Gene with Bipolar Disorder.

ABSTRACT: OBJECTIVE:Circadian rhythms have been linked to psychiatric disorders such as Depression and Bipolar Disorder (BD). Given previous evidences of sleep/circadian disturbances as well as the genetic susceptibility for BD, we decided to investigate the possible link between the PERIOD3 (Per3) circadian gene and BD. METHODS:This is a genetic association case (BD) vs. control study of the Per3 gene. We further subdivided our BD sample into "good sleepers" (PSQI ?5) and "poor sleepers" (PSQI>5) according to the Pittsburgh Sleep Quality Index (PSQI) global score, and then we assessed genetic association of the Per3 gene with sleep quality in the BD group. RESULTS:There were 209 cases and 213 controls in our sample. The GT genotype of the SNP rs707467 significantly associated with BD (?2=8.80; p-value=0.01; adjusted residual=±2.6). We also found significant association of the SNP rs10462020 allele T with BD (?2=5.81; p-value=0.01) as well as the genotype TT (?2= 6.01; p-value=0.04; adjusted residual=±2.4). CONCLUSION:In this study we demonstrated evidences of genetic association between the Per3 gene and BD. The results of association between the Per3 gene and BD in our sample may bring additional evidence to the former findings of association between the Per3 gene and BD.

SUBMITTER: Brasil Rocha PM

PROVIDER: S-EPMC5639137 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Genetic Association of the PERIOD3 (Per3) Clock Gene with Bipolar Disorder.

Brasil Rocha Paulo Marcos PM Campos Simone Becho SB Neves Fernando Silva FS da Silva Filho Humberto Corrêa HC

Psychiatry investigation 20170911 5

<h4>Objective</h4>Circadian rhythms have been linked to psychiatric disorders such as Depression and Bipolar Disorder (BD). Given previous evidences of sleep/circadian disturbances as well as the genetic susceptibility for BD, we decided to investigate the possible link between the PERIOD3 (Per3) circadian gene and BD.<h4>Methods</h4>This is a genetic association case (BD) vs. control study of the Per3 gene. We further subdivided our BD sample into "good sleepers" (PSQI ≤5) and "poor sleepers" ( ...[more]

PMID: 29042894

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Project description:BackgroundBipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP) as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA) and beta (RORB), was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs) in RORA and RORB.MethodsWe genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching.ResultsWe report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs.ConclusionOur findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder.

Dataset Information

Genetic Association of the PERIOD3 (Per3) Clock Gene with Bipolar Disorder.

Publications

Genetic Association of the PERIOD3 (Per3) Clock Gene with Bipolar Disorder.

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