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

作者：Maglione Jeanne E^*; Nievergelt Caroline M; Parimi Neeta; Evans Daniel S; Ancoli Israel Sonia; Stone Katie L; Yaffe Kristine; Redline Susan; Tranah Gregory J

来源：American Journal of Geriatric Psychiatry, 2015, 23(10): 1075-1087.

DOI：10.1016/j.jagp.2015.03.002

• Depression
• older adults
• PER3
• RORA
• circadian
• gene

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. Methods: 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). Results: 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 chi(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 chi(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). Conclusion: PER3 and RORA may play important roles in the development of depressive symptoms in older adults.

• 出版日期2015-10