Polygenic Prediction of Depression Liability Reveals Broad Genetic Associations Across Development, Families, and Populations

Polygenic prediction of depression is limited by the depth of depression phenotyping available at biobank scale as well as sample size. Here we develop a depression score combining information from depression and genetically correlated psychiatric traits using phenotype reconstruction, multi-trait genetic integration and Bayesian effect estimation. Compared with the strongest publicly available depression-only score (Psychiatric Genomics Consortium 2025, excluding 23andMe), the liability-R2 for depression in UK Biobank rose by 49.7% and within-family standardized associations with latent inter

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