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

Authors

Smit RAJ, Wade KH, Hui Q, Arias JD, Yin X, Christiansen MR, Yengo L, Preuss MH, Nakabuye M, Rocheleau G, Graham SE, Buchanan VL, Chittoor G, Graff M, Guindo-Martínez M, Lu Y, Marouli E, Sakaue S, Spracklen CN, Vedantam S, ...show more Wilson EP, Chen SH, Ferreira T, Ji Y, Karaderi T, Lüll K, Machado M, Malden DE, Medina-Gomez C, Moore A, Rüeger S, Akiyama M, Allison MA, Alvarez M, Andersen MK, Appadurai V, Arbeeva L, Bartell E, Bhaskar S, Bielak LF, Bis JC, Bollepalli S, Bork-Jensen J, Bradfield JP, Bradford Y, Brandl C, Braund PS, Brody JA, Broeckel U, Burgdorf KS, Cade BE, Cai Q, Camarda S, Campbell A, Cañadas-Garre M, Chai JF, Chesi A, Choi SH, Christofidou P, Couture C, Cuellar-Partida G, Danning R, Degenhardt F, Delgado GE, Delitala A, Demirkan A, Deng X, Dietl A, Dimitriou M, Dimitrov L, Dorajoo R, Eichelmann F, Eliasen AU, Engmann JE, Erdos MR, Fairhurst-Hunter Z, Farmaki AE, Faul JD, Fernandez-Lopez JC, Forer L, Frank M, Freitag-Wolf S, Fritsche LG, Fuchsberger C, Galesloot TE, Gao Y, Geller F, Giannakopoulou O, Giulianini F, Gjesing AP, Goel A, Gordon SD, Gorski M, Grove J, Guo X, Gustafsson S, Haessler J, Hansen TF, Havulinna AS, Haworth SJ, Heard-Costa N, Hemerich D, Highland HM, Hindy G, Ho YL, Hofer E, Holliday E, Horn K, Hornsby WE, Hottenga JJ, Huang H, Huang J, Huerta-Chagoya A, Huo S, Hwang MY, Hwu CM, Iha H, Ikeda DD, Isono M, Jackson AU, Jansen IE, Jiang Y, Johansson I, Jonsson A, Jørgensen T, Kalafati IP, Kanai M, Kanoni S, Kårhus LL, Kasturiratne A, Katsuya T, Kawaguchi T, Kember RL, Kentistou KA, Kim D, Kim HN, Kim YJ, Kleber ME, Knol MJ, Kurbasic A, Lauzon M, Le P, Lea R, Lee JY, Lee WJ, Leonard HL, Li H, Li SA, Li X, Li X, Liang J, Lin H, Lin K, Liu J, Liu X, Lo KS, Long J, Lores-Motta L, Luan J, Lyssenko V, Lyytikäinen LP, Mahajan A, Malik MZ, Mamakou V, Mangino M, Manichaikul A, Marten J, Mattheisen M, McDaid AF, Mei Q, Meiselbach H, Melendez TL, Milaneschi Y, Miller JE, Millwood IY, Mishra PP, Mitchell RE, Møllehave LT, Mononen N, Mucha S, Munz M, Mykkänen J, Nakatochi M, Nardone GG, Nelson CP, Nethander M, Nho CW, Nielsen AA, Nolte IM, Nongmaithem SS, Noordam R, Ntalla I, Nutile T, Pandit A, Pauper M, Petersen ERB, Petersen LV, Piluso F, Polašek O, Poveda A, Pyarajan S, Raffield LM, Rakugi H, Ramirez J, Rasheed A, Raven D, Rayner NW, Riveros C, Rohde R, Ruggiero D, Ruotsalainen SE, Ryan KA, Sabater-Lleal M, Santin A, Saxena R, Scholz M, Shen B, Shi J, Shin JH, Sidore C, Sidorenko J, Sim X, Slieker RC, Smith AV, Smith JA, Smyth LJ, Southam L, Steinthorsdottir V, Sun L, Takeuchi F, Taylor KD, Tayo BO, Tcheandjieu C, Terzikhan N, Tesolin P, Teumer A, Theusch E, Thompson DJ, Thorleifsson G, Timmers PRHJ, Trompet S, Turman C, Vaccargiu S, van der Laan SW, van der Most PJ, van Klinken JB, van Setten J, Verma SS, Verweij N, Veturi Y, Wang CA, Wang C, Wang JS, Wang L, Wang YX, Wang Z, Warren HR, Bin Wei W, Wen W, Wheeler WA, Wickremasinghe AR, Wielscher M, Winsvold BS, Wong A, Wuttke M, Xia R, Yamamoto K, Yang J, Yao J, Young H, Yousri NA, Yu L, Zeng L, Zhang W, Zhang X, Zhao JH, Zhao W, Zhou W, Zimmermann ME, Zoledziewska M, 't Hart LM, Adair LS, Adams HHH, Aguilar-Salinas CA, Al-Mulla F, Arnett DK, Asselbergs FW, Åsvold BO, Attia J, Banas B, Bandinelli S, Beilin LJ, Bennett DA, Bergler T, Bharadwaj D, Biino G, Boerwinkle E, Böger CA, Borja JB, Bouchard C, Bowden DW, Brandslund I, Brumpton B, Buring JE, Caulfield MJ, Chambers JC, Chandak GR, Chanock SJ, Chaturvedi N, Ida Chen YD, Chen Z, Cheng CY, Cho YS, Christensen K, Christophersen IE, Ciullo M, Cole JW, Collins FS, Concas MP, Cooper RS, Cruz M, Cucca F, Cutler MJ, Damrauer SM, Dantoft TM, de Borst GJ, de Geus EJC, de Groot LCPGM, De Jager PL, de Kleijn DPV, de Silva HJ, Dedoussis GV, den Hollander AI, Du S, Easton DF, Eckardt KU, Elders PJM, Eliassen AH, Ellinor PT, Elmståhl S, Erdmann J, Evans MK, Fatkin D, Feenstra B, Feitosa MF, Ferrucci L, Florez JC, Ford I, Fornage M, Franke A, Franks PW, Freedman BI, Gieger C, Girotto G, Golightly YM, Gonzalez-Villalpando C, Gordon-Larsen P, Grallert H, Grant SFA, Grarup N, Griffiths L, Gudnason V, Haiman C, Hakonarson H, Hansen T, Hartman CA, Hattersley AT, Hayward C, Heid IM, Heng CK, Hengstenberg C, Herzig KH, Hewitt AW, Hishigaki H, Hougaard DM, Hoyng CB, Huang PL, Huang W, Huang WY, Huffman JE, Hunt SC, Hutri N, Hveem K, Hyppönen E, Iacono WG, Ichihara S, Ikram MA, Isasi CR, Jarvelin MR, Jin ZB, Jöckel KH, Jonas JB, Joshi PK, Jousilahti P, Jukema JW, Kähönen M, Kamatani Y, Kang KD, Kaprio J, Kardia SLR, Karpe F, Kato N, Kavousi M, Kee F, Kessler T, Khera AV, Khor CC, Kiemeney LALM, Kim BJ, Kim EK, Kim HL, Kirchhof P, Kivimaki M, Koh WP, Koistinen HA, Kokkinos A, Kooner JS, Kooperberg C, Kovacs P, Kraaijeveld A, Kraft P, Krauss RM, Kumari M, Kutalik Z, Laakso M, Lange LA, Langenberg C, Launer LJ, Lee H, Lee NR, Lehtimäki T, Lemaitre RN, Li H, Li L, Lieb W, Lin X, Lind L, Linneberg A, Liu CT, Liu J, Loeffler M, London B, Lu F, Lubitz SA, Mackey DA, Magnusson PKE, Manson JE, Marcus GM, Marques Vidal P, Martin NG, März W, Matsuda F, McCarthy MI, McGarrah RW, McGue M, McKnight AJ, Medland SE, Mellström D, Metspalu A, Mitchell BD, Mitchell P, Mook-Kanamori DO, Mori TA, Morris AD, Mucci LA, Munroe PB, Nalls MA, Nazarian S, Nelson AE, Neville MJ, Newton-Cheh C, Nielsen CS, Niinikoski H, Nikus K, Nöthen MM, Ogunniyi A, Ohlsson C, Oldehinkel AJ, Orozco L, Pahkala K, Pajukanta P, Palmer CNA, Parra EJ, Pattaro C, Pedersen O, Pennell CE, Penninx BWJH, Perusse L, Peters A, Peyser PA, Porteous DJ, Posthuma D, Power C, Pramstaller PP, Province MA, Psaty BM, Qi Q, Qu J, Rader DJ, Raitakari OT, Rallidis LS, Rao DC, Redline S, Reilly DF, Reiner AP, Rhee SY, Ridker PM, Rienstra M, Ripatti S, Ritchie MD, Rivadeneira F, Roden DM, Rosendaal FR, Rotter JI, Rudan I, Rutters F, Ryu S, Sabanayagam C, Salako B, Saleheen D, Salomaa V, Samani NJ, Sanghera DK, Sattar N, Schmidt B, Schmidt H, Schmidt R, Schulze MB, Schunkert H, Scott LJ, Scott RJ, Sever P, Sheu WHH, Shoemaker MB, Shu XO, Simonsick EM, Sims M, Singleton AB, Sinner MF, Smith JG, Snieder H, Spector TD, Spedicati B, Stampfer MJ, Stark KJ, Strachan DP, Tabara Y, Tai ES, Tang H, Tardif JC, Thanaraj TA, Tönjes A, Tuomi T, Tuomilehto J, Tusié-Luna MT, van Dam RM, van der Harst P, Van der Velde N, van Duijn CM, van Schoor NM, Vitart V, Vohl MC, Völker U, Vollenweider P, Völzke H, Vrieze S, Wacher-Rodarte NH, Walker M, Wander GS, Wareham NJ, Watanabe RM, Watkins H, Weir DR, Werge TM, Widen E, Willemsen G, Willett WC, Wilson JF, Wilson PWF, Wong TY, Woo JT, Wright AF, Xu H, Yajnik CS, Yang J, Yokota M, Yuan JM, Zeggini E, Zemel BS, Zheng W, Zhu X, Zillikens MC, Zonderman AB, Zwart JA, 23andMe Research Team, DiscovEHR (DiscovEHR and MyCode Community Health Initiative), eMERGE (Electronic Medical Records and Genomics Network), GPC-UGR, PRACTICAL Consortium, Understanding Society Scientific Group, VA Million Veteran Program, Abecasis GR, Assimes TL, Auton A, Boehnke M, Chasman DI, Esko T, Stefansson K, Lettre G, Lindgren CM, Ng MCY, O'Donnell CJ, Thorsteinsdottir U, Visscher PM, Walters RG, Winkler TW, Wood AR, Deloukas P, Frayling TM, Justice AE, Kilpeläinen TO, Locke AE, Mohlke KL, North KE, Okada Y, Willer CJ, Young KL, Fatumo S, McCaffery JM, Timpson NJ, Hirschhorn JN, Sun YV, Berndt SI, Loos RJF

Affiliations

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Atlanta VA Health Care System, Decatur, GA, USA.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Department of Public Health, Section of Epidemiology, Algorithmic Fairness Research Group, University of Copenhagen, Copenhagen, Denmark.
Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Department of Population Health Sciences, Geisinger, Danville, PA, USA.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Genetics of Complex Traits, College of Medicine and Health, University of Exeter, Exeter, UK.
Center for Health Data Science, Section for Health Data Science and Artificial Intelligence, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Division of Biostatistics and Epidemiology, RTI International, Durham, NC, USA.
Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
Department of Family Medicine, University of California, San Diego, La Jolla, CA, USA.
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark.
Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Genomic Research on Complex Diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Harvard Medical School, Boston, MA, USA.
Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Centre for Public Health, Queen's University of Belfast, Northern Ireland, UK.
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Department of Kinesiology, Faculty of Medicine, Université Laval, Québec, QC, Canada.
Diamantina Institute, The University of Queensland, Brisbane, Queensland, Australia.
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Dipartimento di Scienze Mediche Chirurgiche e Sperimentali, Università degli Studi di Sassari, Sassari, Italy.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Department of Nutrition Science and Dietetics, School of Health Sciences, University of the Peloponnese, Kalamata, Greece.
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, UK.
Molecular Genetics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Department of Computational Genomics, National Institute of Genomic Medicine, Mexico City, Mexico.
Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany.
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Eurac Research Institute for Biomedicine, Bolzano, Italy.
Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
Jackson Heart Study, Department of Medicine, University of Mississippi, Jackson, MS, USA.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Nuffield Department of Medicine, Centre for Human Genetics, University of Oxford, Oxford, UK.
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Department of Biomedicine (Human Genetics) and iSEQ Center, Aarhus University, Aarhus, Denmark.
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Translational Research Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Veterans Affairs Boston Healthcare System, Boston, MA, USA.
Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
Leipzig University, Medical Faculty, Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany.
Department of Biological Psychology, Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Program in Metabolism and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongwon-gun, Republic of Korea.
Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Biomedical Technology Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
23andMe, Inc., Sunnyvale, CA, USA.
Department of Biobank Research, Umeå University, Umeå, Sweden.
Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Frederiksberg, Denmark.
Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka.
Osaka University Graduate School of Medicine, Osaka, Japan.
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, Scotland.
Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
Department of Computer Science, University of Toronto, Toronto, ON, Canada.
Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Qld University of Technology, Kelvin Grove, Queensland, Australia.
Oneomics, Soonchunhyang Mirai Medical Center, Gyeonggi-do, Republic of Korea.
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Montreal Heart Institute, Montreal, QC, Canada.
Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway.
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
Department of Genetics & Bioinformatics, Dasman Diabetes Institute, Kuwait City, Kuwait.
National and Kapodistrian University of Athens, Dromokaiteio Psychiatric Hospital, Athens, Greece.
Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience Amsterdam UMC/Vrije Universiteit, Amsterdam, The Netherlands.
Biomedical and Translational Informatics Institute, Geisinger, Danville, PA, USA.
Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Institute for Cardiogenetics, University of Lübeck, DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel and University Heart Center Lübeck, Lübeck, Germany.
Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Korea Institute of Science and Technology, Gangneung Institute of Natural Products, Gangneung, Republic of Korea.
Department of Clinical Biochemistry, Lillebaelt Hospital, Kolding, Denmark.
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Naples, Italy.
Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Medical School, University of Split, Šoltanska 2, Split, Croatia.
Center for Non-Communicable Diseases, Karachi, Pakistan.
Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
Department of Medicine, Division of Endocrinology, Diabetes & Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
Unit of Genomics of Complex Diseases, Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain.
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Department of Biomedical Science, Hallym University, Chuncheon, Republic of Korea.
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Cagliari, Italy.
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Department of Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA.
VA Palo Alto Health Care System, Palo Alto, CA, USA.
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Cardiology Division, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Central Diagnostic Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, USA.
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.
Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Information Management Services, Inc., Calverton, UK.
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, University College London, London, UK.
Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Japan.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar.
Department of Cardiology, German Heart Centre Munich, Technical University Munich, Munich, Germany.
Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.
Department of Cardiology, Amsterdam Cardiovascular Sciences Institute, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Geriatric Unit, Azienda Toscana Centro, Florence, Italy.
Medical School, Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia.
Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University (JNU), New Delhi, India.
Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy.
Human Genetics Center and Department of Epidemiology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines.
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Danish Aging Research Center, University of Southern Denmark, Odense, Denmark.
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Department of Neurology, Division of Vascular Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.
Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Intermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.
Department of Vascular Surgery, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Department of General Practice, Amsterdam Public Health Institute, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
German Center for Diabetes Research (DZD), Neuherberg, Germany.
Centro de Investigacion en Salud Poblacional Instituto Nacional de Salud Publica and Centro de Estudios en Diabetes, Cuernavaca Morelos, Mexico.
Icelandic Heart Association, Kopavogur, Iceland.
Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA.
Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK.
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
Research Unit of Biomedicine and Internal Medicine, Biocenter of Oulu, Medical Research Center, University of Oulu, Oulu, Finland.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Department of Congenital Disorders and Danish National Biobank, Statens Serum Institut, Copenhagen, Denmark.
Department of Genetics, Shanghai-MOST Key Laboratory of Heath and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute, Shanghai, China.
Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
Australian Centre for Precision Health, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan.
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Institut Français de Myopie, Hôpital Fondation Rothschild, Paris, France.
Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
Department of Ophthalmology, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Republic of Korea.
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK.
Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Department of Cardiology, University Heart and Vascular Center UKE Hamburg, Hamburg, Germany.
UCL Brain Sciences, University College London, London, UK.
Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Department of Cardiology, Ealing Hospital, London North West University Healthcare NHS Trust, Middlesex, UK.
Medical Department III - Endocrinology, Nephrology, Rheumatology, Leipzig University Medical Center, Leipzig, Germany.
Institute for Social and Economic Research, University of Essex, Wivenhoe Park, UK.
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Department of Medicine, University of Colorado at Denver, Aurora, CO, USA.
Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing, China.
Institute of Epidemiology and Biobank Popgen, Kiel University, Kiel, Germany.
Division of Cardiovascular Medicine and Abboud Cardiovascular Research Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, China.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Division of Cardiology, University of California, San Francisco, San Francisco, CA, USA.
Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Centre for Vision Research and Department of Ophthalmology, Westmead Millennium Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Electrophysiology Section, Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway.
Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, Finland.
Institute of Human Genetics, School of Medicine & University Hospital Bonn, Bonn, Germany.
Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, CDMX, Mexico City, Mexico.
Pat MacPherson Centre for Pharmacogenetics and Pharmacogenomics, Division of Population Health and Genomics, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada.
Population, Policy and Practice, UCL Great Ormond Street Hospital Institute of Child Health, London, UK.
Second Department of Cardiology, Medical School, National and Kapodistrian University of Athens, University General Hospital Attikon, Athens, Greece.
Center for Biostatistics and Data Science, Washington University School of Medicine, St. Louis, MO, USA.
Genetics, Merck Sharp & Dohme Corp., Kenilworth, NJ, USA.
Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Dongdaemun-gu, Seoul, Republic of Korea.
Departments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Epidemiology and Data Science, Amsterdam Public Health Institute, Amsterdam Cardiovascular Sciences Institute, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Department of Medicine, University of Ibadan, Ibadan, Nigeria.
Department of Pediatrics, Section of Genetics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Gottfried Schatz Research Center (for Cell Signaling, Metabolism and Aging), Medical University of Graz, Graz, Austria.
Deutsches Herzzentrum München, Cardiology, Deutsches Zentrum für Herz- und Kreislaufforschung (DZHK) - Munich Heart Alliance and Technische Universität München, München, Germany.
School of Biomedical Science and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
National Heart and Lung Institute, Imperial College London, London, UK.
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Social Medicine, Population and Public Health, School of Medicine, University of California, Riverside, Riverside, CA, USA.
German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.
Population Health Research Institute, St. George's University of London, London, UK.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Department of Epidemiology and Data Science, Amsterdam UMC, Amsterdam, The Netherlands.
Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods, Université Laval, Québec, QC, Canada.
DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
Unidad de Investigación Médica en Epidemiología Clínica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Hero DMC Heart Institute, Dayanand Medical College, Ludhiana, India.
Department of Population and Public Health Sciences, Keck School of Medicine of USC, Los Angeles, CA, USA.
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Diabetes Unit, KEM Hospital and Research Centre, Pune, India.
School of Life Sciences, Westlake University, Hangzhou, China.
Kurume University School of Medicine, Kurume, Japan.
Cancer Epidemiology and Prevention Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
McDonnell Genome Institute and Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
Precision Healthcare University Research Institute, Queen Mary University of London, London, UK.
Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ruth.loos@sund.ku.dk.

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.

Publication Details

PubMed ID
40691366

Digital Object Identifier
10.1038/s41591-025-03827-z

Publication
Nat Med. 2025 Sep; Volume 31 (Issue 9): Pages 3151-3168

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