Clinical trajectories and genetic architecture across the neurological-psychiatric boundary

Neurological and psychiatric disorders are treated as distinct diagnostic categories, yet genetic studies reveal substantial pleiotropy between them. Whether this overlap extends to clinical trajectories has not been tested at scale. We compared disease trajectory embeddings from Delphi-2M, a transformer model trained only on the health records of 400,000 UK Biobank participants, with genome-wide genetic correlations across 19 neurological and psychiatric disorders. Clinical and genetic similarity partly converged across disorder pairs (Mantel r = 0.33). Both measures placed most disorders closer to their own diagnostic category than to the other. Both also made the same three exceptions: multiple sclerosis, migraine, and essential tremor sat closer on average to psychiatric than to neurological disorders. Clinical trajectories and genetic architecture thus draw the same diagnostic boundary and break it in the same places. These findings support a more integrated approach to neurological and psychiatric disorders.