TY - JOUR T1 - A polygenic risk score associated with measures of depressive symptoms among older adults. JF - Biodemography Soc Biol Y1 - 2014 A1 - Morgan E. Levine A1 - Eileen M. Crimmins A1 - Carol A Prescott A1 - Drystan F. Phillips A1 - Thalida E. Arpawong A1 - Jinkook Lee KW - Aged KW - Aged, 80 and over KW - Depressive Disorder, Major KW - Female KW - Genetic Predisposition to Disease KW - Genetic Variation KW - Genome-Wide Association Study KW - Humans KW - Male KW - Middle Aged KW - Multifactorial Inheritance KW - Odds Ratio KW - Risk Factors AB -

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.

PB - 60 VL - 60 IS - 2 N1 - Times Cited: 0 SI 0 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25343367?dopt=Abstract U2 - PMC4298361 U4 - GENOME-WIDE ASSOCIATION/INDIVIDUAL GENETIC RISK/MAJOR DEPRESSION/DISEASE RISK/HERITABILITY/genetics/genetics/depression/Depressive Symptoms/CES Depression Scale/CES Depression Scale/regression Analysis ER -