Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps,Nature Medicine

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Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps
Nature Medicine ( IF 58.7 ) Pub Date : 2021-11-15 , DOI: 10.1038/s41591-021-01549-6
Adebowale Adeyemo ₁ , Charles N. Rotimi ₁ , Mary K. Balaconis ₂ , Deanna R. Darnes ₃ , Segun Fatumo _{4,

5,

6} , Palmira Granados Moreno ₇ , Bartha M. Knoppers ₇ , Chani J. Hodonsky ₈ , Michael Inouye _{9,

10,

11,

12,

13,

14,

15} , Masahiro Kanai _{16,

17,

18,

19} , Alicia R. Martin _{16,

17,

18} , Samuli Ripatti _{16,

18,

20,

21} , Yukinori Okada ₁₉ , Kazuto Kato ₂₂ , Anna C. F. Lewis ₂₃ , Mark I. McCarthy ₂₄ , Michelle N. Meyer ₂₅ , J. Brent Richards _{26,

27,

28} , Lucas Richter ₂₉ , Elisabeth Widen ₂₁ , Saskia C. Sanderson _{30,

31,

32} , Amy C. Sturm ₃₃ , Ricardo A. Verdugo _{34,

35} , Cristen J. Willer _{36,

37,

38} , Genevieve L. Wojcik ₃₉ , Alicia Zhou ₄₀

Affiliation

Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, MD, USA
Broad Institute of Harvard and MIT, Cambridge, MA, USA
Genetic Counselling Services, Fetal Care Center Dallas, Dallas, TX, USA
London School of Hygiene and Tropical Medicine, London, UK
Uganda Medical Informatics Centre (UMIC), MRC/UVRI and LSHTM (Uganda Research Unit), Entebbe, Uganda
H3Africa Bioinformatics Network (H3ABioNet) Node, Center for Genomics Research and Innovation (CGRI)/National Biotechnology Development Agency CGRI/NABDA, Abuja, Nigeria
Centre of Genomics and Policy, Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Canada
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
British Heart Foundation Cambridge Centre of Research Excellence, School of Clinical Medicine, University of Cambridge, Cambridge, UK
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK
National Institute for Health Research Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
The Alan Turing Institute, London, UK
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
Department of Public Health, Clinicum, University of Helsinki, Helsinki, Finland
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Biomedicum 2U, Helsinki, Finland
Department of Biomedical Ethics and Public Policy, Graduate School of Medicine, Osaka University, Suita, Japan
E J Safra Center for Ethics, Harvard University, Cambridge, MA, USA
Genentech, South San Francisco, CA, USA
Center for Translational Bioethics and Health Care Policy, Geisinger, Danville, PA, USA
Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada
Department of Human Genetics, McGill University, Montreal, Canada
Vanderbilt University School of Medicine, Nashville, TN, USA
Department of Behavioural Science and Health, University College London, London, UK
Our Future Health, London, UK
PHG Foundation, Cambridge, UK
Genomic Medicine Institute, Geisinger, Danville, PA, USA
Human Genetics Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile
Department of Basic-Clinical Oncology, Faculty of Medicine, Santiago, Chile
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Color Genomics, Burlingame, CA, USA

Polygenic risk scores (PRSs) aggregate the many small effects of alleles across the human genome to estimate the risk of a disease or disease-related trait for an individual. The potential benefits of PRSs include cost-effective enhancement of primary disease prevention, more refined diagnoses and improved precision when prescribing medicines. However, these must be weighed against the potential risks, such as uncertainties and biases in PRS performance, as well as potential misunderstanding and misuse of these within medical practice and in wider society. By addressing key issues including gaps in best practices, risk communication and regulatory frameworks, PRSs can be used responsibly to improve human health. Here, the International Common Disease Alliance’s PRS Task Force, a multidisciplinary group comprising expertise in genetics, law, ethics, behavioral science and more, highlights recent research to provide a comprehensive summary of the state of polygenic score research, as well as the needs and challenges as PRSs move closer to widespread use in the clinic.

中文翻译：

在临床中负责任地使用多基因风险评分：潜在的好处、风险和差距

多基因风险评分 (PRS) 汇总了人类基因组中等位基因的许多微小影响，以估计个体患疾病或疾病相关性状的风险。PRS 的潜在好处包括具有成本效益的初级疾病预防增强、更精细的诊断和提高开药时的精确度。然而，必须权衡这些潜在风险，例如 PRS 绩效的不确定性和偏见，以及在医疗实践和更广泛的社会中对这些的潜在误解和误用。通过解决关键问题，包括最佳实践、风险沟通和监管框架方面的差距，PRS 可以负责任地用于改善人类健康。在这里，国际常见疾病联盟的 PRS 工作组是一个多学科小组，包括遗传学、法律、伦理学、

更新日期：2021-11-16

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