title: Associations of PER3 and RORA Circadian Gene Polymorphisms and Depressive Symptoms in Older Adults.
abstract: BACKGROUND
  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 χ2=-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 χ2=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).
  
  
  CONCLUSIONS
  PER3 and RORA may play important roles in the development of depressive symptoms in older adults.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA. Electronic address: jmaglione@ucsd.edu.
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Maglione
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Nievergelt
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA.
authors.forename: Neeta
authors.initials: N
authors.lastname: Parimi
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Evans
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA; Department of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ancoli-Israel
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Stone
authors.affiliation: Departments of Psychiatry, Neurology, and Epidemiology, University of California, San Francisco, CA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tranah
mesh_terms: D056044:Actigraphy; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003863:Depression / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics*; D016017:Odds Ratio; D056950:Period Circadian Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors
chemical_list: D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C512644:PER3 protein, human; D056950:Period Circadian Proteins; C539738:RORA protein, human
keywords: Depression; PER3; RORA; circadian; gene; older adults