Deep learning–based integration of genetics with registry data for stratification of schizophrenia and depression

Author:

Allesøe Rosa Lundbye12ORCID,Nudel Ron13ORCID,Thompson Wesley K.345ORCID,Wang Yunpeng6ORCID,Nordentoft Merete137,Børglum Anders D.389,Hougaard David M.310ORCID,Werge Thomas347ORCID,Rasmussen Simon2ORCID,Benros Michael Eriksen1311ORCID

Affiliation:

1. Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.

2. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

3. iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.

4. Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.

5. Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, San Diego, CA, USA.

6. Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo, Forskningsveien 3A, 0317 Oslo, Norway.

7. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

8. Department of Biomedicine, Aarhus University and Centre for Integrative Sequencing, iSEQ, Aarhus, Denmark.

9. Aarhus Genome Center, Aarhus, Denmark.

10. Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

11. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

Currently, psychiatric diagnoses are, in contrast to most other medical fields, based on subjective symptoms and observable signs and call for new and improved diagnostics to provide the most optimal care. On the basis of a deep learning approach, we performed unsupervised patient stratification of 19,636 patients with depression [major depressive disorder (MDD)] and/or schizophrenia (SCZ) and 22,467 population controls from the iPSYCH2012 case cohort. We integrated data of disorder severity, history of mental disorders and disease comorbidities, genetics, and medical birth data. From this, we stratified the individuals in six and seven unique clusters for MDD and SCZ, respectively. When censoring data until diagnosis, we could predict MDD clusters with areas under the curve (AUCs) of 0.54 to 0.80 and SCZ clusters with AUCs of 0.71 to 0.86. Overall cases and controls could be predicted with an AUC of 0.81, illustrating the utility of data-driven subgrouping in psychiatry.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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