Gene set enrichment analysis to create polygenic scores: a developmental examination of aggression

Abstract

Previous approaches for creating polygenic risk scores (PRSs) do not explicitly consider the biological or developmental relevance of the genetic variants selected for inclusion. We applied gene set enrichment analysis to meta-GWAS data to create developmentally targeted, functionally informed PRSs. Using two developmentally matched meta-GWAS discovery samples, separate PRSs were formed, then examined in time-varying effect models of aggression in a second, longitudinal sample of children (n = 515, 49% female) in early childhood (2–5 years old), and middle childhood (7.5–10.5 years old). Functional PRSs were associated with aggression in both the early and middle childhood models.