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Associations of PER3 and RORA Circadian Gene Polymorphisms and Depressive Symptoms in Older Adults.

ABSTRACT: Depressive symptoms are common in older adults and associated with poor outcomes. Although circadian genes have been implicated in depression, the relationship between circadian genes and depressive symptoms in older adults is unclear.A cross-sectional genetic association study of 529 single nucleotide polymorphisms (SNPs) representing 30 candidate circadian genes was performed in two population-based cohorts: the Osteoporotic Fractures in Men Study (MrOS; N=270, age: 76.58±5.61 years) and the Study of Osteoporotic Fractures (SOF) in women (N=1740, 84.05±3.53 years) and a meta-analysis was performed. Depressive symptoms were assessed with the Geriatric Depression Scale categorizing participants as having none-few symptoms (0-2), some depressive symptoms (>2 to <6), or many depressive symptoms (?6).We found associations meeting multiple testing criteria for significance between the PER3 intronic SNP rs12137927 and decreased odds of reporting "some depressive symptoms" in the SOF sample (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.48-0.78, df=1, Wald ?2=-4.04, p=0.000054) and the meta-analysis (OR: 0.61, CI: 0.48-0.78, z=-4.04, p=0.000054) and between the PER3 intronic SNPs rs228644 (OR: 0.74, CI: 0.63-0.86, z=3.82, p=0.00013) and rs228682 (OR: 0.74, CI: 0.86-0.63, z=3.81, p=0.00014) and decreased odds of reporting "some depressive symptoms" in the meta-analysis compared to endorsing none-few depressive symptoms. The RORA intronic SNP rs11632098 was associated with greater odds of reporting "many depressive symptoms" (OR: 2.16, CI: 1.45-3.23, df=1, Wald ?2=3.76, p=0.000168) in the men. In the meta-analysis the association was attenuated and nominally significant (OR: 1.63, CI: 1.24-2.16, z=3.45, p=0.00056).PER3 and RORA may play important roles in the development of depressive symptoms in older adults.

SUBMITTER: Maglione JE

PROVIDER: S-EPMC4568170 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Associations of PER3 and RORA Circadian Gene Polymorphisms and Depressive Symptoms in Older Adults.

Maglione Jeanne E JE Nievergelt Caroline M CM Parimi Neeta N Evans Daniel S DS Ancoli-Israel Sonia S Stone Katie L KL Yaffe Kristine K Redline Susan S Tranah Gregory J GJ

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20150313 10

<h4>Background</h4>Depressive symptoms are common in older adults and associated with poor outcomes. Although circadian genes have been implicated in depression, the relationship between circadian genes and depressive symptoms in older adults is unclear.<h4>Methods</h4>A cross-sectional genetic association study of 529 single nucleotide polymorphisms (SNPs) representing 30 candidate circadian genes was performed in two population-based cohorts: the Osteoporotic Fractures in Men Study (MrOS; N=27 ...[more]

PMID: 25892098

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Project description:Depression and its related mood disorders are a major global health issue that disproportionately affects young adults. A number of factors that influence depressive symptoms are particularly relevant to the young adult developmental stage, including sleep loss, poor sleep quality, and the tendency toward eveningness in circadian preferences. However, relatively few studies have examined the relationship between sleep and circadian phenotypes, and their respective influences on mood, or considered potential molecular mechanisms driving these associations. Here, we use a multi-year, cross-sectional study of 806 primarily undergraduates to examine the relationships between sleep-wake chronotype, sleep disturbance, depression and genotypes associated with the PER3 variable number of tandom repeats (VNTR) polymorphism-circadian gene variants associated with both chronotype and sleep homeostatic drive. In addition, we use objective, Fitbit-generated sleep structure data on a subset of these participants (n = 67) to examine the relationships between chronotype, depression scores, actual measures of sleep duration, social jetlag, and the percent of deep and rapid eye movement (REM) sleep per night. In this population, chronotype is weakly associated with depressive symptoms and moderately correlated with self-reported sleep disturbance. Sleep disturbance is significantly associated with depression scores, but objective sleep parameters are not directly correlated with Beck Depression Inventory (BDI-II) scores, with the exceptions of a moderate correlation between social jetlag and depression scores in females and a marginal correlation between sleep duration and depression scores. Multiple regression and path analyses reveal that chronotype effects on depressive symptoms in this population are mediated largely by sleep disturbance. The PER3 VNTR genotype significantly predicts depressive symptoms in a model with objective sleep parameters, but it does not significantly predict depressive symptoms in a model with chronotype or subjective sleep disturbance. Interestingly, PER35,5 genotypes, in males only, are independently related to chronotype and depression scores. Our results support hypotheses linking subjective sleep quality and chronotype and provide a first step in understanding how objective sleep structure may be linked to chronotype and depressive symptoms. Our results also suggest that circadian gene variants may show sex-specific effects linking sleep duration and sleep structure to depression.

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Dataset Information

Associations of PER3 and RORA Circadian Gene Polymorphisms and Depressive Symptoms in Older Adults.

Publications

Associations of PER3 and RORA Circadian Gene Polymorphisms and Depressive Symptoms in Older Adults.

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