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Precision medicine in complex diseases—Molecular subgrouping for improved prediction and treatment stratification
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopment Research, University of Oslo, Oslo, Norway.
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Rigshospitalet, Blegdamsvej 9, Copenhagen University Hospital, Copenhagen, Denmark.
Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Science, Lund University, Lund, Sweden; Novo Nordisk Foundation, Hellerup, Denmark.
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2023 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 294, no 4, p. 378-396Article, review/survey (Refereed) Published
Abstract [en]

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease—both with regards to symptoms and underlying causal mechanisms—and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases—including psychiatric disorders and allergies—available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023. Vol. 294, no 4, p. 378-396
Keywords [en]
complex diseases, genetic variations, genomic medicine, GWAS, molecular profiling, multi omics, polygenic risk score (PRS), precision medicine
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-208069DOI: 10.1111/joim.13640ISI: 000974676300001PubMedID: 37093654Scopus ID: 2-s2.0-85153517541OAI: oai:DiVA.org:umu-208069DiVA, id: diva2:1760127
Funder
Swedish Research Council, 2019-01497Swedish Research Council, 2016-0386Swedish Research Council, 2018-05619Swedish Heart Lung Foundation, 20200687Swedish Heart Lung Foundation, 20210546Swedish Heart Lung Foundation, 20210519Swedish Heart Lung Foundation, 20200693The Swedish Brain FoundationSwedish Cancer Society, 22 2222 PjNovo Nordisk Foundation, NF17OC002759Novo Nordisk Foundation, NNF14CC001Novo Nordisk Foundation, NF20OC005931Available from: 2023-05-29 Created: 2023-05-29 Last updated: 2024-03-26Bibliographically approved

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Hedman, Harald

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