Polygenic prediction of body mass index and obesity through the life course and across ancestries

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from age 2.5 years to adolescence, with earlier adiposity rebound. Adding the PGS to predictors available at birth nearly doubled explained variance for BMI from age 5 onward (for example, from 11% to 21% at age 8). Up to age 5, adding the PGS to early-life BMI improved prediction of BMI at age 18 (for example, from 22% to 35% at age 5). Higher PGSs were associated with greater adult weight gain. In intensive lifestyle intervention trials, individuals with higher PGSs lost modestly more weight in the first year (0.55 kg per s.d.) but were more likely to regain it. Overall, these data show that PGSs have the potential to improve obesity prediction, particularly when implemented early in life.

Publication Details

Journal
Apollo (University of Cambridge)
Published
2024-10-31
Primary Topic
Genetic Associations and Epidemiology
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article

Polygenic prediction of body mass index and obesity through the life course and across ancestries

Apollo (University of Cambridge)
Genetic Associations and Epidemiology
article

Polygenic prediction of body mass index and obesity through the life course and across ancestries

article en

Abstract

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from age 2.5 years to adolescence, with earlier adiposity rebound. Adding the PGS to predictors available at birth nearly doubled explained variance for BMI from age 5 onward (for example, from 11% to 21% at age 8). Up to age 5, adding the PGS to early-life BMI improved prediction of BMI at age 18 (for example, from 22% to 35% at age 5). Higher PGSs were associated with greater adult weight gain. In intensive lifestyle intervention trials, individuals with higher PGSs lost modestly more weight in the first year (0.55 kg per s.d.) but were more likely to regain it. Overall, these data show that PGSs have the potential to improve obesity prediction, particularly when implemented early in life.

Apollo (University of Cambridge)
National Science Foundation, Foundation for the National Institutes of Health, Cancer Research Institute, Prostate Cancer Foundation, Juvenile Diabetes Research Foundation International, March of Dimes Foundation, Breast Cancer Research Foundation, Ovarian Cancer Research Fund, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Bayer, GlaxoSmithKline, Sanofi, Atlantic Philanthropies, Yale University, Gilead Sciences, Alexion Pharmaceuticals, Children's Hospital of Philadelphia, University of Pennsylvania, Victor Chang Cardiac Research Institute, University of Michigan, Hjerteforeningen, Foundation for Cardiovascular Research, Danone, Helsingin Yliopisto, University of Notre Dame, Case Western Reserve University, Takeda Pharmaceutical Company, Helsingin ja Uudenmaan Sairaanhoitopiiri, Boston Scientific Corporation, Deutsches Krebsforschungszentrum, National Cancer Research Institute, Movember Foundation, Genome Canada, Japan Agency for Medical Research and Development, Pancreatic Cancer UK, Regeneron Pharmaceuticals, Yrjö Jahnssonin Säätiö, Finska Läkaresällskapet, Wellcome Trust, Deutsches Zentrum für Herz-Kreislaufforschung, United Kingdom Clinical Research Collaboration, Scottish Government, Royal Marsden NHS Foundation Trust, National Center for Global Health and Medicine, Swedish Cancer Foundation, NorthShore University HealthSystem, Broad Institute, Government of the United Kingdom, Australian Government, Leidos, Folkhälsanin Tutkimussäätiö, Health~Holland, Fondation du cancer du sein du Québec, Department for the Economy, Janssen Scientific Affairs, Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen, Cotswold Foundation, Amsterdam University Medical Centers, Jan Dekker Stichting, Invitae, Government of Canada, Prostate Cancer Canada, National Institute for Health and Care Research, British Heart Foundation, Scottish Funding Council, University of Cambridge, European Commission, Rosetrees Trust, Queen's University Belfast, University of Bristol, Prostate Cancer Foundation of Australia, Women and Infants Research Foundation, National Research Foundation, Agency for Science, Technology and Research, National University of Singapore, National Research Foundation Singapore, Council of Scientific and Industrial Research, India, Centre for Ageing Research and Development in Ireland, Science Foundation Ireland, Public Health Agency, Deutsche Forschungsgemeinschaft, Fondation Leducq, Ministry of Education, Culture, Sports, Science and Technology, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universiteit Leiden, Rijksuniversiteit Groningen, Stiftelsen för Strategisk Forskning, Danmarks Grundforskningsfond, Murdoch University, University of Notre Dame Australia, National Natural Science Foundation of China, Radboud Universiteit, Vrije Universiteit Amsterdam, National Science Council, Kela, Bundesministerium für Bildung und Forschung, Austrian Science Fund, Sungkyunkwan University, Generalitat de Catalunya, Gentofte Hospital, Dalhousie University, Nierstichting, Else Kröner-Fresenius-Stiftung, Suomen Kulttuurirahasto, Fonds Wetenschappelijk Onderzoek, Consejo Nacional de Ciencia y Tecnología, Ministero della Salute, Lunds Universitet, Nederlandse Zuivel Organisatie, Queen's University, Ministero dell’Istruzione, dell’Università e della Ricerca, Lundbeckfonden, University of Toronto, Korea Institute of Science and Technology, National Research Foundation of Korea, Regione Campania, Juho Vainion Säätiö, Karolinska Institutet, Oesterreichische Nationalbank, Knut och Alice Wallenbergs Stiftelse, Universität zu Lübeck, Novo Nordisk, Signe ja Ane Gyllenbergin Säätiö, Stockholms Läns Landsting, Office of the First Minister and Deputy First Minister, National Health Research Institutes, Emil Aaltosen Säätiö, Samfundet Folkhälsan, Ministerio de Ciencia e Innovación, Instituto Mexicano del Seguro Social, Umeå Universitet, Augustinus Fonden, Universitetet i Bergen, Leids Universitair Medisch Centrum, Universitair Medisch Centrum Groningen, National and Kapodistrian University of Athens, Universitätsklinikum Regensburg, Fundación IMSS, Dasman Diabetes Institute, Norges Forskningsråd, Turun Yliopisto, Sydäntutkimussäätiö, Universität Hamburg, Ludwig-Maximilians-Universität München, Lastentautien Tutkimussäätiö, Göteborgs Universitet, Deutsche Herzstiftung, Deutsche Krebshilfe, Center for Translational Molecular Medicine, Department of Health, Government of Western Australia, Oulun Yliopisto, Radboud Universitair Medisch Centrum, Institut National Du Cancer, Tampereen Tuberkuloosisäätiö, National Institute of Biomedical Innovation, Otsuka Pharmaceutical, Medical Research Council Canada, TrygFonden, Gratama Stichting, Wetenschappelijk Onderzoek- en Documentatiecentrum, Diabetesliitto, Paavo Nurmen Säätiö, Karl-Franzens-Universität Graz, Safe Work Australia, Faculty of Health and Medical Sciences, University of Western Australia, Oogfonds, Novo Nordisk Fonden, Chinese Society of Clinical Oncology, Egmont Fonden, Taichung Veterans General Hospital, Medizinische Universität Graz, Landelijke Stichting voor Blinden en Slechtzienden, Stichting Blindenhulp, Tays, University of Thessaly, Syöpäsäätiö, Government of Western Australia, Skånes universitetssjukhus, University of Kelaniya, Siemens Healthineers, Servier, National University Health System, Turun Yliopistollinen Keskussairaala, Vlaamse regering, Mitsubishi Tanabe Pharma Corporation, Fondation Institut de Cardiologie de Montréal, Institut de Cardiologie de Montréal, Hjartavernd, H. Lundbeck A/S, Diabetestutkimussäätiö, Xarxa de Bancs de Tumors de Catalunya, Freistaat Sachsen, Provincia autonoma di Bolzano - Alto Adige, KfH-Stiftung Präventivmedizin, Vincent Fairfax Family Foundation, Heinz Nixdorf Stiftung, Diabetesforeningen, Fundación Marqués de Valdecilla, Amsterdam Neuroscience, Sygehus Lillebælt, Turun Yliopistosäätiö, National Institutes of Health, Centers for Disease Control and Prevention, Samsung, Perelman School of Medicine, University of Pennsylvania, Wake Forest School of Medicine, Abbott Diagnostics, Helsinki Institute of Life Science, Helsingin Yliopisto, Elizabeth Blackwell Institute for Health Research, University of Bristol, Canadian Institutes of Health Research, Canadian Cancer Society Research Institute, Medical Research Council, Economic and Social Research Council, Cancer Council Victoria, National Medical Research Council, Korea National Institute of Health, Instituto de Salud Carlos III, Wageningen University and Research, Sahlgrenska Akademin, Helse Sør-Øst RHF, Det Sundhedsvidenskabelige Fakultet, Københavns Universitet, Departament d'Universitats, Recerca i Societat de la Informació, Health and Social Care Research and Development Division, National Key Research and Development Program of China, China-Japan Friendship Hospital, Biomedical Research Council, Helmholtz Zentrum München, Faculty of Medicine and Health, University of Sydney, National Institute on Aging, National Cancer Institute, Biosense Webster, UCB Pharma, Institute of Genetics, Core Research for Evolutional Science and Technology, Center of Innovation Program, JST-Mirai Program
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Genetic Associations and Epidemiology
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