The utility of obesity polygenic risk scores from research to clinical practice: A review

Author:

Jansen Philip R.1234ORCID,Vos Niels12,van Uhm Jorrit12,Dekkers Ilona A.5,van der Meer Rieneke67ORCID,Mannens Marcel M. A. M.12,van Haelst Mieke M.128

Affiliation:

1. Amsterdam UMC, Department of Human Genetics University of Amsterdam Amsterdam Netherlands

2. Amsterdam Reproduction and Development Research Institute Amsterdam Netherlands

3. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research VU University Amsterdam Netherlands

4. Netherlands Institute for Neuroscience Amsterdam Netherlands

5. Department of Radiology Leiden University Medical Center Leiden Netherlands

6. Netherlands Obesity Clinic Huis ter Heide Netherlands

7. Amsterdam UMC, Department of Endocrinology and Metabolism University of Amsterdam Amsterdam Netherlands

8. Amsterdam UMC, Emma Center for Personalized Medicine University of Amsterdam Amsterdam Netherlands

Abstract

SummaryObesity represents a major public health emergency worldwide, and its etiology is shaped by a complex interplay of environmental and genetic factors. Over the last decade, polygenic risk scores (PRS) have emerged as a promising tool to quantify an individual's genetic risk of obesity. The field of PRS in obesity genetics is rapidly evolving, shedding new lights on obesity mechanisms and holding promise for contributing to personalized prevention and treatment. Challenges persist in terms of its clinical integration, including the need for further validation in large‐scale prospective cohorts, ethical considerations, and implications for health disparities. In this review, we provide a comprehensive overview of PRS for studying the genetics of obesity, spanning from methodological nuances to clinical applications and challenges. We summarize the latest developments in the generation and refinement of PRS for obesity, including advances in methodologies for aggregating genome‐wide association study data and improving PRS predictive accuracy, and discuss limitations that need to be overcome to fully realize its potential benefits of PRS in both medicine and public health.

Funder

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Publisher

Wiley

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