Contrasting Broad- and Clinically- defined Polygenic Indicators of Depression and Depression-related Phenotypes in Adults and Children

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- (PGSBD) and clinical- (PGSMDD) depression summary statistics from the UK Biobank using a sample of adults (N=210; 100% European Ancestry) who have been extensively phenotyped for depression and related neurocognitive traits (e.g., rumination, emotion regulation, anhedonia, and resting frontal alpha asymmetry). PGS associations with depression severity and diagnosis were generally modest (β’s ranging from 0.150 (PGSMDD on current depression diagnosis) to 0.177 (PGS PGSBD on current depression diagnosis)). Overall, the UK Biobank-derived broad-depression PGS had a small but significant association with suicidal ideation (such that higher PGSBD was associated with suicidal ideation) but its association with other neurocognitive variables was minimal. The UK Biobank-derived MDD PGS had limited transportability to endo/intermediary phenotypes measured in this study.