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 8,761 participants from the Health and Retirement Study (HRS). Polygenic scores were derived from the Psychiatric Genomics Consortium (PGC) genome-wide association study (GWAS) of MDD. SLEs were operationalized as a dichotomous variable indicating whether participants had experienced at least 1 stressful event during the previous two years. Depressive symptoms were measured using an 8-item CES-D subscale and operationalized as both a dichotomous and a count variable. Results The odds of reporting ≥ 4 depressive symptoms were over twice as high among individuals who experienced at least one SLE (OR = 2.19, 95% CI = [1.86, 2.58]). Polygenic scores were significantly associated with depressive symptoms (β = .21, p = <.0001), although the variance explained was modest (Pseudo r2 = .0095). None of the interaction terms for polygenic scores and SLEs were 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.

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…Previous studies using this approach found that a genome-wide polygenic score was able to explain only small percentages of the variance in depression; for example, 1% was reported in elderly cohorts (Demirkan et al 2011;Musliner et al 2015) and 0.2%when considering a long-term average depression score (Chang et al 2014). Phenotypic and environmental heterogeneity may explain these low percentages, but the available evidence excluded that stressful life events may interact with PRS associated with depression (Musliner et al 2015).…”

“…Phenotypic and environmental heterogeneity may explain these low percentages, but the available evidence excluded that stressful life events may interact with PRS associated with depression (Musliner et al 2015). However, PRS were reported to have higher effect sizes as depressive symptom severity increased (Chang et al 2014).…”

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

“…Specifically, the penetrance of polygenic loading for MDD was greater among those with a history of childhood trauma. A US population-based study of older adults (N = 8761) found no interaction between the MDD PRS and recent stressful life events on depressive symptoms, though the life events measure was limited and the outcome measure (CES-D) captures only current symptoms (Musliner et al, 2014).…”

Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women

“…The current study explores the genetic risk underlying both severe forms of mental illness – recurrent MDD, bipolar disorder, schizophrenia, and anxiety disorders – and traits that have been previously associated with MDD, but do not represent clinically significant outcomes (Hettema et al 2006; Musliner et al 2015; Okbay et al 2016): neuroticism, depressive symptoms, and subjective well-being. Genetic relationships within the former set have been examined widely within samples of European descent (Hettema, 2008; Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013; Cross-Disorder Group of the Psychiatric Genomics Consortium et al , 2013).…”