title: Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis.
abstract: BACKGROUND
  Previous studies suggest that the relationship between genetic risk and depression may be moderated by stressful life events (SLEs). The goal of this study was to assess whether SLEs moderate the association between polygenic risk of major depressive disorder (MDD) and depressive symptoms in older adults.
  
  
  METHODS
  We used logistic and negative binomial regressions to assess the associations between polygenic risk, SLEs and depressive symptoms in a sample of 8761 participants from the Health and Retirement Study. Polygenic scores were derived from the Psychiatric Genomics Consortium genome-wide association study of MDD. SLEs were operationalized as a dichotomous variable indicating whether participants had experienced at least one stressful event during the previous 2 years. Depressive symptoms were measured using an eight-item Center for Epidemiologic Studies Depression Scale subscale and operationalized as both a dichotomous and a count variable.
  
  
  RESULTS
  The odds of reporting four or more depressive symptoms were over twice as high among individuals who experienced at least one SLE (odds ratio 2.19, 95% confidence interval 1.86-2.58). Polygenic scores were significantly associated with depressive symptoms (β = 0.21, p ⩽ 0.0001), although the variance explained was modest (pseudo r 2 = 0.0095). None of the interaction terms for polygenic scores and SLEs was statistically significant.
  
  
  CONCLUSIONS
  Polygenic risk and SLEs are robust, independent predictors of depressive symptoms in older adults. Consistent with an additive model, we found no evidence that SLEs moderated the association between common variant polygenic risk and depressive symptoms.
authors.affiliation: Department of Mental Health,Bloomberg School of Public Health,Johns Hopkins University,Baltimore,MD,USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Musliner
authors.affiliation: Department of Psychiatry and Behavioral Sciences,Johns Hopkins Institute of Medicine,Baltimore,MD,USA.
authors.forename: F
authors.initials: F
authors.lastname: Seifuddin
authors.affiliation: Department of Psychiatry and Behavioral Sciences,Johns Hopkins Institute of Medicine,Baltimore,MD,USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Judy
authors.affiliation: Department of Psychiatry and Behavioral Sciences,Johns Hopkins Institute of Medicine,Baltimore,MD,USA.
authors.forename: M
authors.initials: M
authors.lastname: Pirooznia
authors.affiliation: Department of Psychiatry and Behavioral Sciences,Johns Hopkins Institute of Medicine,Baltimore,MD,USA.
authors.forename: F S
authors.initials: FS
authors.lastname: Goes
authors.affiliation: Department of Mental Health,Bloomberg School of Public Health,Johns Hopkins University,Baltimore,MD,USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Zandi
mesh_terms: D003863:Depression / Q000453:epidemiology / Q000235:genetics; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D016017:Odds Ratio; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
keywords: stress