Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score.

Autor:	Ritchie SC; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; 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.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK., Taylor HJ; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Liang Y; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore., Manikpurage HD; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK., Pennells L; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK., Foguet C; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK., Abraham G; Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.; Department of Clinical Pathology, University of Melbourne, Parkville, Victoria, Australia., Gibson JT; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK., Jiang X; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, US., Liu Y; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; 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.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK., Xu Y; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK., Kim LG; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK., Mahajan A; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN.; OMNI Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA., McCarthy MI; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN.; OMNI Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA., Kaptoge S; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK., Lambert SA; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Wood A; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.; Cambridge Centre of Artificial Intelligence in Medicine, University of Cambridge, Cambridge, UK., Sim X; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore., Collins FS; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Denny JC; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.; All of Us Research Program, National Institutes of Health, Bethesda, MD, USA., Danesh J; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.; Department of Human Genetics, Wellcome Sanger Institute, Hinxton, UK., Butterworth AS; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK., Di Angelantonio E; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.; Health Data Science Research Centre, Human Technopole, Milan, Italy., Inouye M; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; 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.; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Sep 23. Date of Electronic Publication: 2024 Sep 23.
DOI:	10.1101/2024.08.22.24312440
Abstrakt:	Combining information from multiple GWASs for a disease and its risk factors has proven a powerful approach for development of polygenic risk scores (PRSs). This may be particularly useful for type 2 diabetes (T2D), a highly polygenic and heterogeneous disease where the additional predictive value of a PRS is unclear. Here, we use a meta-scoring approach to develop a metaPRS for T2D that incorporated genome-wide associations from both European and non-European genetic ancestries and T2D risk factors. We evaluated the performance of this metaPRS and benchmarked it against existing genome-wide PRS in 620,059 participants and 50,572 T2D cases amongst six diverse genetic ancestries from UK Biobank, INTERVAL, the All of Us Research Program, and the Singapore Multi-Ethnic Cohort. We show that our metaPRS was the most powerful PRS for predicting T2D in European population-based cohorts and had comparable performance to the top ancestry-specific PRS, highlighting its transferability. In UK Biobank, we show the metaPRS had stronger predictive power for 10-year risk than all individual risk factors apart from BMI and biomarkers of dysglycemia. The metaPRS modestly improved T2D risk stratification of QDiabetes risk scores for 10-year risk prediction, particularly when prioritising individuals for blood tests of dysglycemia. Overall, we present a highly predictive and transferrable PRS for T2D and demonstrate that the potential for PRS to incrementally improve T2D risk prediction when incorporated into UK guideline-recommended screening and risk prediction with a clinical risk score. Competing Interests: Competing Interests During the course of this project G.A. became a full-time employee of CSL Ltd. All significant contributions to this study were made prior to this role and CSL Ltd had no input to the study. A.M. and M.I.M are both employees of Genentech Ltd, and holders of Roche stock. Genentech Ltd was not involved with the described work. J.D. serves on scientific advisory boards for AstraZeneca, Novartis, and UK Biobank, and has received multiple grants from academic, charitable and industry sources outside of the submitted work. A.S.B. reports institutional grants from AstraZeneca, Bayer, Biogen, BioMarin, Bioverativ, Novartis, Regeneron and Sanofi. M.I. is a trustee of the Public Health Genomics (PHG) Foundation, a member of the Scientific Advisory Board of Open Targets, and has research collaborations with AstraZeneca, Nightingale Health and Pfizer which are unrelated to this study. The remaining authors declare no competing interests.
Databáze:	MEDLINE
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