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 ages 50+ from the Health and Retirement Study (HRS). Depressive symptoms were measured by 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<10−05 to generate a weighted PRS for our replication sample (n=3,091). Results showed the PRS was significantly associated with mean CESD score in the replication sample (β=.08, P=.002). The R2-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% 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 increase an individual’s susceptibility for chronically experiencing high levels of depressive symptoms.

Polygenic Risk Scores in Clinical Psychology: Bridging Genomic Risk to Individual Differences

“…Of note, PRS derived from GWAS of other psychopathologies (e.g., depression) do not currently account for nearly as much variance in disorder expression (Levine et al, 2014). However, it is expected that sample sizes for discovery GWAS will continue to increase, and with that, there will be greater precision in the effect sizes that are used as weights, and, consequently, the proportion of variance that they explain.…”

Differential Vulnerability to Early-Life Parental Death: The Moderating Effects of Family Suicide History on Risks for Major Depression and Substance Abuse in Later Life

“…Neither have we identified any study examining early-life interactions on outcomes measured in later adulthood, despite indications that heritable factors are still impactful at advanced ages (Kim et al 2014, Levine et al 2014). We suspect the dearth of inquiry may partially be due to difficulties in procuring sufficient data.…”

Clozapine as a Model for Antipsychotic Development

“…From a clinical perspective, the greater the PRS, the higher the disease risk. PRS are obtained by selecting single-nucleotide polymorphisms (SNPs) associated with a phenotype of interest from GWAS samples and creating a sum of their phenotype associated alleles [86,88]. This is important because many SNPs may not meet genome-wide significance alone, but together they may be significant.…”