Polygenic overlap of physical activity with schizophrenia and Parkinson's disease

Polygenic overlap between objectively measured physical activity and schizophrenia and Parkinson’s disease is substantial despite negligible genetic correlations (rg=-0.02–0.02, p>0.05).

• Why it matters: Shared genetic architecture could clarify whether physical activity can serve as a digital biomarker across psychiatric and neurological disorders, but overlap with schizophrenia and PD is unclear.
• What they did: The study used GWAS of objectively measured physical activity (n=89,683) plus multi-trait GWAS with self-reported activity (n=124,842–377,234), then cross-trait analyses with schizophrenia (n=53,386 cases, 77,258 controls) and PD (63,555 cases, 17,700 proxy cases, 1,746,386 controls).
• The result: Convergent methods (causal mixture modelling, local genetic correlations, and conjunctional false discovery rate) showed shared variants with mixed effect directions; shared genes with schizophrenia were differentially expressed in the amygdala and basal ganglia and linked to cognitive-affective traits, while shared genes with PD related to neurodegenerative disorders and structural brain phenotypes.

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