Associating broad and clinically defined polygenic scores for depression with depression-related phenotypes

Abstract

Twin studies indicate that 30-40% of the disease liability for depression can be attributed to genetic differences. Here, we assess the explanatory ability of polygenic scores (PGS) based on broad- (PGS_BD) and clinical- (PGS_MDD) depression summary statistics from the UK Biobank in an independent sample of adults (N = 210; 100% European Ancestry) who were extensively phenotyped for depression and related neurocognitive traits (e.g., rumination, emotion regulation, anhedonia, and resting frontal alpha asymmetry). The UK Biobank-derived PGS_BD had small associations with MDD, depression severity, anhedonia, cognitive reappraisal, brooding, and suicidal ideation but only the association with suicidal ideation remained statistically significant after correcting for multiple comparisons. Similarly small associations were observed for the PGS_MDD but none remained significant after correcting for multiple comparisons. These findings provide important initial guidance about the expected effect sizes between current UKB PGSs for depression and depression-related neurocognitive phenotypes.