Artificial intelligence for dementia genetics and omics

Author:

Bettencourt Conceicao12ORCID,Skene Nathan34,Bandres‐Ciga Sara5,Anderson Emma6,Winchester Laura M.7,Foote Isabelle F.8,Schwartzentruber Jeremy91011,Botia Juan A.12,Nalls Mike513,Singleton Andrew514,Schilder Brian M.34,Humphrey Jack15,Marzi Sarah J.34,Toomey Christina E.21617,Kleifat Ahmad Al18,Harshfield Eric L.19,Garfield Victoria20,Sandor Cynthia21,Keat Samuel21,Tamburin Stefano22,Frigerio Carlo Sala23,Lourida Ilianna24,Ranson Janice M.24,Llewellyn David J.2425,

Affiliation:

1. Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology London UK

2. Queen Square Brain Bank for Neurological Disorders UCL Queen Square Institute of Neurology London UK

3. UK Dementia Research Institute Imperial College London London UK

4. Department of Brain Sciences Imperial College London London UK

5. Center for Alzheimer's and Related Dementias (CARD) National Institute on Aging and National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland USA

6. Department of Mental Health of Older People Division of Psychiatry University College London London UK

7. Department of Psychiatry University of Oxford Oxford UK

8. Institute for Behavioral Genetics University of Colorado Boulder Boulder Colorado USA

9. Open Targets Cambridge UK

10. Wellcome Sanger Institute Cambridge UK

11. Illumina Artificial Intelligence Laboratory Illumina Inc Foster City California USA

12. Departamento de Ingeniería de la Información y las Comunicaciones Universidad de Murcia Murcia Spain

13. Data Tecnica International LLC Washington, DC USA

14. Laboratory of Neurogenetics National Institute on Aging National Institutes of Health Bethesda Maryland USA

15. Nash Family Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai New York USA

16. Department of Clinical and Movement Neuroscience UCL Queen Square Institute of Neurology London UK

17. The Francis Crick Institute London UK

18. Department of Basic and Clinical Neuroscience Maurice Wohl Clinical Neuroscience Institute Institute of Psychiatry Psychology and Neuroscience King's College London London UK

19. Stroke Research Group Department of Clinical Neurosciences University of Cambridge Cambridge UK

20. MRC Unit for Lifelong Health and Ageing Institute of Cardiovascular Science University College London London UK

21. UK Dementia Research Institute. School of Medicine Cardiff University Cardiff UK

22. Department of Neurosciences Biomedicine and Movement Sciences, Neurology Section University of Verona Verona Italy

23. UK Dementia Research Institute Queen Square Institute of Neurology University College London London UK

24. University of Exeter Medical School Exeter UK

25. The Alan Turing Institute London UK

Abstract

AbstractGenetics and omics studies of Alzheimer's disease and other dementia subtypes enhance our understanding of underlying mechanisms and pathways that can be targeted. We identified key remaining challenges: First, can we enhance genetic studies to address missing heritability? Can we identify reproducible omics signatures that differentiate between dementia subtypes? Can high‐dimensional omics data identify improved biomarkers? How can genetics inform our understanding of causal status of dementia risk factors? And which biological processes are altered by dementia‐related genetic variation? Artificial intelligence (AI) and machine learning approaches give us powerful new tools in helping us to tackle these challenges, and we review possible solutions and examples of best practice. However, their limitations also need to be considered, as well as the need for coordinated multidisciplinary research and diverse deeply phenotyped cohorts. Ultimately AI approaches improve our ability to interrogate genetics and omics data for precision dementia medicine.Highlights We have identified five key challenges in dementia genetics and omics studies. AI can enable detection of undiscovered patterns in dementia genetics and omics data. Enhanced and more diverse genetics and omics datasets are still needed. Multidisciplinary collaborative efforts using AI can boost dementia research.

Funder

National Institute on Aging

Multiple System Atrophy Trust

ALS Association

NIHR Maudsley Biomedical Research Centre

Alzheimer's Society

Diabetes UK

British Heart Foundation

Diabetes Research and Wellness Foundation

Medical Research Council

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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