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A polygenic risk score associated with measures of depressive symptoms among older adults.

ABSTRACT: It has been suggested that depression is a polygenic trait, arising from the influences of multiple loci with small individual effects. The aim of this study is to generate a polygenic risk score (PRS) to examine the association between genetic variation and depressive symptoms. Our analytic sample included N = 10,091 participants aged 50 and older from the Health and Retirement Study (HRS). Depressive symptoms were measured by Center for Epidemiological Studies-Depression scale (CESD) scores assessed on up to nine occasions across 18 years. We conducted a genome-wide association analysis for a discovery set (n = 7,000) and used the top 11 single-nucleotide polymorphisms, all with p < 10(-5) to generate a weighted PRS for our replication sample (n = 3,091). Results showed that the PRS was significantly associated with mean CESD score in the replication sample (? = .08, p = .002). The R(2) change for the inclusion of the PRS was .003. Using a multinomial logistic regression model, we also examined the association between genetic risk and chronicity of high (4+) CESD scores. We found that a one-standard-deviation increase in PRS was associated with a 36 percent increase in the odds of having chronically high CESD scores relative to never having had high CESD scores. Our findings are consistent with depression being a polygenic trait and suggest that the cumulative influence of multiple variants increases an individual's susceptibility for chronically experiencing high levels of depressive symptoms.

SUBMITTER: Levine ME

PROVIDER: S-EPMC4298361 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A polygenic risk score associated with measures of depressive symptoms among older adults.

Levine Morgan E ME Crimmins Eileen M EM Prescott Carol A CA Phillips Drystan D Arpawong Thalida E TE Lee Jinkook J

Biodemography and social biology 20140101 2

It has been suggested that depression is a polygenic trait, arising from the influences of multiple loci with small individual effects. The aim of this study is to generate a polygenic risk score (PRS) to examine the association between genetic variation and depressive symptoms. Our analytic sample included N = 10,091 participants aged 50 and older from the Health and Retirement Study (HRS). Depressive symptoms were measured by Center for Epidemiological Studies-Depression scale (CESD) scores as ...[more]

PMID: 25343367

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Project description:Depression has been identified as a risk factor for dementia. However, most studies have measured depressive symptoms at only one time point, and older adults may show different patterns of depressive symptoms over time.To investigate the association between trajectories of depressive symptoms and risk of dementia in older adults.This was a prospective cohort investigation of black and white community-dwelling older adults in the Health, Aging, and Body Composition study. Participants were enrolled between May 1997 and June 1998 and followed up through 2001-2002. The dates of this analysis were September 2014 to December 2015. The setting was community research centers in Memphis, Tennessee, and Pittsburgh, Pennsylvania. Trajectories of depressive symptoms were assessed from baseline to year 5. Symptoms were measured with the Center for Epidemiologic Studies Depression Scale Short Form, and trajectories were calculated using latent class growth curve analysis.Incident dementia through year 11, determined by dementia medication use, hospital records, or significant cognitive decline (?1.5 SD race-specific decline on the Modified Mini-Mental State Examination). We examined the association between depressive symptom trajectories and dementia incidence using Cox proportional hazards regression models adjusted for demographics, health factors that differed between groups, and cognition during the depressive symptom assessment period (baseline to year 5).The analytic cohort included 2488 black and white older adults with repeated depressive symptom assessments from baseline to year 5 who were free of dementia throughout that period. Their mean (SD) age at baseline was 74.0 (2.8) years, and 53.1% (n?=?1322) were female. The following 3 depressive symptom trajectories were identified: consistently minimal symptoms (62.0% [n?=?1542] of participants), moderate and increasing symptoms (32.2% [n?=?801] of participants), and high and increasing symptoms (5.8% [n?=?145] of participants). Compared with the consistently minimal trajectory, having a high and increasing depressive symptom trajectory was associated with significantly increased risk of dementia (fully adjusted hazard ratio, 1.94; 95% CI, 1.30-2.90), while the moderate and increasing trajectory was not associated with risk of dementia after full adjustment. Sensitivity analyses indicated that the high and increasing trajectory was associated with dementia incidence, while depressive symptoms at individual time points were not.Older adults with a longitudinal pattern of high and increasing depressive symptoms are at high risk for dementia. Individuals' trajectory of depressive symptoms may inform dementia risk more accurately than one-time assessment of depressive symptoms.

Dataset Information

A polygenic risk score associated with measures of depressive symptoms among older adults.

Publications

A polygenic risk score associated with measures of depressive symptoms among older adults.

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