TY - JOUR
T1 - Responsible use of polygenic risk scores in the clinic
T2 - potential benefits, risks and gaps
AU - Polygenic Risk Score Task Force of the International Common Disease Alliance
AU - Adeyemo, Adebowale
AU - Balaconis, Mary K.
AU - Darnes, Deanna R.
AU - Fatumo, Segun
AU - Granados Moreno, Palmira
AU - Hodonsky, Chani J.
AU - Inouye, Michael
AU - Kanai, Masahiro
AU - Kato, Kazuto
AU - Knoppers, Bartha M.
AU - Lewis, Anna C.F.
AU - Martin, Alicia R.
AU - McCarthy, Mark I.
AU - Meyer, Michelle N.
AU - Okada, Yukinori
AU - Richards, J. Brent
AU - Richter, Lucas
AU - Ripatti, Samuli
AU - Rotimi, Charles N.
AU - Sanderson, Saskia C.
AU - Sturm, Amy C.
AU - Verdugo, Ricardo A.
AU - Widen, Elisabeth
AU - Willer, Cristen J.
AU - Wojcik, Genevieve L.
AU - Zhou, Alicia
N1 - Funding Information:
The spouse of C.J.W. works at Regeneron Pharmaceuticals. J.B.R. has served as an advisor to GlaxoSmithKline and Deerfield Capital. His institution has received investigator-initiated grant funding from Eli Lilly, GlaxoSmithKline, and Biogen for projects unrelated to this research. He is the founder of 5 Prime Sciences. M.M. is an employee of Genentech and a holder of Roche stock.
Funding Information:
We are grateful to the International Common Disease Alliance (ICDA). In particular, we acknowledge the leadership of E. Lander, C. Lindgren, M. Daly, and R. Liao, the ICDA Ethics & Policy Working Group and its co-chairs C. Hutter and M. Zawati, and the administrative support of A. Trankiem. We are also grateful to T. Gjorgjieva for research assistance. Funding: C.J.W. is supported by NIH grants HL135824, HL109946, and HL127564. A.R.M. is supported by NIH grant R00 MH117229. Y.O. is supported by JSPS KAKENHI (19H01021 and 20K21834) and AMED (JP21km0405211, JP21ek0109413, JP21gm4010006, JP21km0405217, JP21ek0410075), JST Moonshot R&D (JPMJMS2021). S.R. is supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers 312062 and 336820) and Horizon 2020 Research and Innovation Programme (grant number 101016775 ‘INTERVENE’). B.M.K. and P.G.M. are supported by the PERSPECTIVE I&I project, which is funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministère de l’Économie et de l’Innovation du Québec through Genome Québec, the Quebec Breast Cancer Foundation, the CHU de Quebec Foundation and the Ontario Research Fund. B.M.K. is supported by the Canada Research Chair in Law and Medicine. M.N.M. is supported by Open Philanthropy (010623-00001), the Russell Sage Foundation and the JPB Foundation (1903-13498), and National Institute on Aging (R01AG042568-04 and R24AG065184). The Richards research group is supported by the Canadian Institutes of Health Research (CIHR: 365825; 409511, 100558, 169303), the McGill Interdisciplinary Initiative in Infection and Immunity (MI4), the Lady Davis Institute of the Jewish General Hospital, the Jewish General Hospital Foundation, the Canadian Foundation for Innovation, the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, McGill University, Cancer Research UK (grant number C18281/A29019), and the Fonds de Recherche Québec Santé (FRQS). J.B.R. is supported by a FRQS Mérite Clinical Research Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, Medical Research Council, European Union, the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. These funding agencies had no role in the design, implementation, or interpretation of this study. M.I. is supported by the Munz Chair of Cardiovascular Prediction and Prevention. This study was supported by the Victorian Government’s Operational Infrastructure Support (OIS) program and by core funding from: the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. The support of the UK Economic and Social Research Council (ESRC) is gratefully acknowledged (ES/T013192/1). S.F. is funded by the Wellcome International Intermediate fellowship (220740/Z/20/Z) at the MRC/UVRI and LSHTM. S.F. is funded by the Wellcome International Intermediate fellowship (220740/Z/20/Z) at the MRC/UVRI and LSHTM. R.A.V. is supported by ANID Chile (FONDEF D10E1007, FONDECYT 1191948, COVID0961). R.A.V. is supported by ANID Chile (FONDEF D10E1007, FONDECYT 1191948, COVID0961).
Publisher Copyright:
© 2021, Springer Nature America, Inc.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85119596771&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119596771&partnerID=8YFLogxK
U2 - 10.1038/s41591-021-01549-6
DO - 10.1038/s41591-021-01549-6
M3 - Review article
C2 - 34782789
AN - SCOPUS:85119596771
SN - 1078-8956
VL - 27
SP - 1876
EP - 1884
JO - Nature Medicine
JF - Nature Medicine
IS - 11
ER -