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

Integrating depression with genetically correlated internalizing traits increases UK Biobank depression liability prediction by 49.7% versus the best depression-only score, while within-family links to latent internalizing rise up to 54%.

• Why it matters: Depression polygenic prediction is constrained by shallow biobank phenotyping and limited sample sizes, leaving uncertainty about whether broader internalizing genetics can improve prediction without losing specificity or family-level validity.
• What they did: The authors built an integrated depression score using phenotype reconstruction, multi-trait genetic integration, and Bayesian effect estimation, then compared it to the strongest depression-only score (excluding 23andMe) in UK Biobank and tested it across ABCD outcomes.
• The result: In ABCD, the integrated score’s association profile across 2,328 childhood/adolescent outcomes matches depression-only (r = 0.99) but is uniformly stronger, including within-family effects (423 outcomes), and it predicts suicidal thoughts and substance use, with stronger symptom associations in girls and attenuation by genetic distance in Hispanic and African American children.

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