Specificity of Polygenic Scores for Psychiatric Disorders Beyond Transdiagnostic Genetic Risk

To what extent do polygenic scores for psychiatric disorders index transdiagnostic rather than disorder-specific genetic risk?In this cohort study of 6567 young adults in the UK, the polygenic score showed at least comparable associations with psychiatric outcomes compared with the corresponding uncorrected polygenic scores. Disorder-specific polygenic scores showed attenuated associations, although a small number retained significant disorder-specific risks.These findings suggest that polygenic scores may primarily reflect genetic liability shared across psychiatric disorders, emphasizing the need to disentangle transdiagnostic and disorder-specific signals to improve interpretability and clinical relevance.

Corresponding Author: Engin Keser, MSc, Social, Genetic, and Developmental Psychiatry Centre, King’s College London, Memory Ln, London SE5 8AF, United Kingdom (engin.keser@kcl.ac.uk).

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