title: 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 (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.
authors.affiliation: a Davis School of Gerontology , University of Southern California , Los Angeles , California , USA.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Levine
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Crimmins
authors.forename: Carol A
authors.initials: CA
authors.lastname: Prescott
authors.forename: Drystan
authors.initials: D
authors.lastname: Phillips
authors.forename: Thalida E
authors.initials: TE
authors.lastname: Arpawong
authors.forename: Jinkook
authors.initials: J
authors.lastname: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003865:Major Depressive Disorder / Q000235:genetics* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000523:psychology; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D016017:Odds Ratio; D012307:Risk Factors