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

TitleA polygenic risk score associated with measures of depressive symptoms among older adults.
Publication TypeJournal Article
Year of Publication2014
AuthorsLevine, ME, Crimmins, EM, Prescott, CA, Phillips, DF, Arpawong, TE, Lee, J
JournalBiodemography Soc Biol
Volume60
Issue2
Pagination199-211
Date Published2014
ISSN Number1948-5573
KeywordsAged, Aged, 80 and over, Depressive Disorder, Major, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Multifactorial Inheritance, Odds Ratio, Risk Factors
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 (β = .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.

Notes

Times Cited: 0 SI 0

DOI10.1080/19485565.2014.952705
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/25343367?dopt=Abstract

Endnote Keywords

GENOME-WIDE ASSOCIATION/INDIVIDUAL GENETIC RISK/MAJOR DEPRESSION/DISEASE RISK/HERITABILITY/genetics/genetics/depression/Depressive Symptoms/CES Depression Scale/CES Depression Scale/regression Analysis

Endnote ID

999999

Alternate JournalBiodemography Soc Biol
Citation Key8057
PubMed ID25343367
PubMed Central IDPMC4298361
Grant ListU01 AG009740 / AG / NIA NIH HHS / United States
T32 AG000037 / AG / NIA NIH HHS / United States
F32AG048681 / AG / NIA NIH HHS / United States
P30AG017265 / AG / NIA NIH HHS / United States
R01 AG030153 / AG / NIA NIH HHS / United States
T32AG0037 / AG / NIA NIH HHS / United States
P30 AG017265 / AG / NIA NIH HHS / United States
R01AG030153 / AG / NIA NIH HHS / United States
F32 AG048681 / AG / NIA NIH HHS / United States