Work

Clinical trajectories and genetic architecture across the neurological–psychiatric boundary

Year: 2026

Type: preprint

Abstract: 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.

Source: medRxiv

DOI: 10.64898/2026.08.06.26359855

Authors: J. Kopal, O.B. Smeland, E. Hagen, A. Amanzadi, B. Erdos, J. Fuhrer, A. Shadrin, O. Frei, D. van der Meer, K.S. O’Connell, A.M. Dale, O.A. Andreassen

Institutions: Oslo University Hospital, University of Oslo, J. Craig Venter Institute, University of California San Diego

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: European Commission, Universitetet i Oslo, Norges Forskningsråd, National Institutes of Health, HORIZON EUROPE Framework Programme, Helse Sør-Øst RHF, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse

Awards: G1160300623, G1300865376, G1332954518, Modern Signal Processing Methods for Ultra-realistic Light-Field Displays, G1692236560, Psych-STRATA - A Stratified Treatment Algorithm in Psychiatry: A program on stratified pharmacogenomics in severe mental illness, G2084491167, G2230720350, G225017805, G2547880585, G304045356, G3096137445, G3761261155, G4949420144, G5034484810, G5351531748, G5479941350, G6185609362, G6517481153, G6966598969, Predicting comorbid cardiovascular disease in individuals with mental disorder by decoding disease mechanisms, G7714202236, G7984825499, Using real-world big data from eHealth, biobanks and national registries, integrated with clinical trial data to improve outcome of severe mental disorders, The VETSA Longitudinal MRI Twin Study of Aging (VETSA MRI 4), Healthy Brain and Child Development National Consortium Data Coordinating Center, ABCD-USA Consortium: Data Analysis, Informatics and Resource Center, OTA-21-015A Post-Acute Sequelae of SARS-CoV-2 Infection Initiative: NYU Langone Health Clinical Science Core, Data Resource Core, and PASC Biorepository Core

OpenAlex ID: W7202071079

Cites: 19

Cited by:

Related to: 10