Polygenic Prediction of Body Mass Index and Obesity Through the Life Course and Across Ancestries.

Details

• Alternative Title:
  Nature Medicine, 2025, v. 31, no. 9: Polygenic Prediction of Body Mass Index and Obesity Through the Life Course and Across Ancestries.
• Journal Article:
  Nature Medicine
• Personal Author:
  Smit, Roelof A. J. ; Wade, Kaitlin H. ; Hui, Qin ; Arias, Joshua D. ; Yin, Xianyong ; Christiansen, Malene R. ; Yengo, Loic ; Preuss, Michael H. ; Nakabuye, Mariam ; Rocheleau, Ghislain ; Graham, Sarah E. ; Buchanan, Victoria L. ; Chittoor, Geetha ; Graff, Marielisa ; Guindo-Martínez, Marta ; Lu, Yingchang ; Marouli, Eirini ; Sakaue, Saori ; Spracklen, Cassandra N. ; Vedantam, Sailaja ; Wilson, Emma P. ; Chen, Shyh-Huei ; Ferreira, Teresa ; Ji, Yingjie ; Karaderi, Tugce ; Lüll, Kreete ; Machado, Moara ; Malden, Deborah E. ; Medina-Gomez, Carolina ; Moore, Amy ; Rüeger, Sina ; Akiyama, Masato ; Allison, Matthew A. ; Alvarez, Marcus ; Andersen, Mette K. ; Appadurai, Vivek ; Arbeeva, Liubov ; Bartell, Eric ; Bhaskar, Seema ; Bielak, Lawrence F. ; Bis, Joshua C. ; Bollepalli, Sailalitha ; Bork-Jensen, Jette ; Bradfield, Jonathan P. ; Bradford, Yuki ; Brandl, Caroline ; Braund, Peter S. ; Brody, Jennifer A. ; Broeckel, Ulrich ; Burgdorf, Kristoffer S. ; Cade, Brian E. ; Cai, Qiuyin ; Camarda, Silvia ; Campbell, Archie ; Cañadas-Garre, Marisa ; Chai, Jin-Fang ; Chesi, Alessandra ; Choi, Seung Hoan ; Christofidou, Paraskevi ; Couture, Christian ; Cuellar-Partida, Gabriel ; Danning, Rebecca ; Degenhardt, Frauke ; Delgado, Graciela E. ; Delitala, Alessandro ; Demirkan, Ayşe ; Deng, Xuan ; Dietl, Alexander ; Dimitriou, Maria ; Dimitrov, Latchezar ; Dorajoo, Rajkumar ; Eichelmann, Fabian ; Eliasen, Anders U. ; Engmann, Jorgen E. ; Erdos, Michael R. ; Fairhurst-Hunter, Zammy ; Farmaki, Aliki-Eleni ; Faul, Jessica D. ; Fernandez-Lopez, Juan-Carlos ; Forer, Lukas ; Frank, Mirjam ; Freitag-Wolf, Sandra ; Fritsche, Lars G. ; Fuchsberger, Christian ; Galesloot, Tessel E. ; Gao, Yan ; Geller, Frank ; Giannakopoulou, Olga ; Giulianini, Franco ; Gjesing, Anette P. ; Goel, Anuj ; Gordon, Scott D. ; Gorski, Mathias ; Grove, Jakob ; Guo, Xiuqing ; Gustafsson, Stefan ; Haessler, Jeffrey ; Hansen, Thomas F. ; Havulinna, Aki S. ; Haworth, Simon J. ; Heard-Costa, Nancy ; Hemerich, Daiane ; Highland, Heather M. ; Hindy, George ; Ho, Yuk-Lam ; Hofer, Edith ; Holliday, Elizabeth ; Horn, Katrin ; Hornsby, Whitney E. ; Hottenga, Jouke-Jan ; Huang, Hongyan ; Huang, Jie ; Huerta-Chagoya, Alicia ; Huo, Shaofeng ; Hwang, Mi Yeong ; Hwu, Chii-Min ; Iha, Hiroyuki ; Ikeda, Daisuke D. ; Isono, Masato ; Jackson, Anne U. ; Jansen, Iris E. ; Jiang, Yunxuan ; Johansson, Ingegerd ; Jonsson, Anna ; Jørgensen, Torben ; Kalafati, Ioanna P. ; Kanai, Masahiro ; Kanoni, Stavroula ; Kårhus, Line L. ; Kasturiratne, Anuradhani ; Katsuya, Tomohiro ; Kawaguchi, Takahisa ; Kember, Rachel L. ; Kentistou, Katherine A. ; Kim, Daeeun ; Kim, Han-Na ; Kim, Young Jin ; Kleber, Marcus E. ; Knol, Maria J. ; Kurbasic, Azra ; Lauzon, Marie ; Le, Phuong ; Lea, Rodney ; Lee, Jong-Young ; Lee, Wen-Jane ; Leonard, Hampton L. ; Li, Hengtong ; Li, Shengchao A. ; Li, Xiaohui ; Li, Xiaoyin ; Liang, Jingjing ; Lin, Honghuang ; Lin, Kuang ; Liu, Jun ; Liu, Xueping ; Lo, Ken Sin ; Long, Jirong ; Lores-Motta, Laura ; Luan, Jian'an ; Lyssenko, Valeriya ; Lyytikäinen, Leo-Pekka ; Mahajan, Anubha ; Malik, Md Zubbair ; Mamakou, Vasiliki ; Mangino, Massimo ; Manichaikul, Ani ; Marten, Jonathan ; Mattheisen, Manuel ; McDaid, Aaron F. ; Mei, Quanshun ; Meiselbach, Heike ; Melendez, Tori L. ; Milaneschi, Yuri ; Miller, Jason E. ; Millwood, Iona Y. ; Mishra, Pashupati P. ; Mitchell, Ruth E. ; Møllehave, Line T. ; Mononen, Nina ; Mucha, Sören ; Munz, Matthias ; Mykkänen, Juha ; Nakatochi, Masahiro ; Nardone, Giuseppe Giovanni ; Nelson, Christopher P. ; Nethander, Maria ; Nho, Chu Won ; Nielsen, Aneta A. ; Nolte, Ilja M. ; Nongmaithem, Suraj S. ; Noordam, Raymond ; Ntalla, Ioanna ; Nutile, Teresa ; Pandit, Anita ; Pauper, Marc ; Petersen, Eva R. B. ; Petersen, Liselotte V. ; Piluso, Francesco ; Polašek, Ozren ; Poveda, Alaitz ; Pyarajan, Saiju ; Raffield, Laura M. ; Rakugi, Hiromi ; Ramirez, Julia ; Rasheed, Asif ; Raven, Dennis ; Rayner, Nigel W. ; Riveros, Carlos ; Rohde, Rebecca ; Ruggiero, Daniela ; Ruotsalainen, Sanni E. ; Ryan, Kathleen A. ; Sabater-Lleal, Maria ; Santin, Aurora ; Saxena, Richa ; Scholz, Markus ; Shen, Botong ; Shi, Jingchunzi ; Shin, Jae Hun ; Sidore, Carlo ; Sidorenko, Julia ; Sim, Xueling ; Slieker, Roderick C. ; Smith, Albert V. ; Smith, Jennifer A. ; Smyth, Laura J. ; Southam, Lorraine ; Steinthorsdottir, Valgerdur ; Sun, Liang ; Takeuchi, Fumihiko ; Taylor, Kent D. ; Tayo, Bamidele O. ; Tcheandjieu, Catherine ; Terzikhan, Natalie ; Tesolin, Paola ; Teumer, Alexander ; Theusch, Elizabeth ; Thompson, Deborah J. ; Thorleifsson, Gudmar ; Timmers, Paul R. H. J. ; Trompet, Stella ; Turman, Constance ; Vaccargiu, Simona ; van der Laan, Sander W. ; van der Most, Peter J. ; van Klinken, Jan B. ; van Setten, Jessica ; Verma, Shefali S. ; Verweij, Niek ; Veturi, Yogasudha ; Wang, Carol A. ; Wang, Chaolong ; Wang, Jun-Sing ; Wang, Lihua ; Wang, Ya Xing ; Wang, Zhe ; Warren, Helen R. ; Wei, Wen Bin ; Wen, Wanqing ; Wheeler, William A. ; Wickremasinghe, Ananda R. ; Wielscher, Matthias ; Winsvold, Bendik S. ; Wong, Andrew ; Wuttke, Matthias ; Xia, Rui ; Yamamoto, Ken ; Yang, Jingyun ; Yao, Jie ; Young, Hannah ; Yousri, Noha A. ; Yu, Lei ; Zeng, Lingyao ; Zhang, Weihua ; Zhang, Xinyuan ; Zhao, Jing-Hua ; Zhao, Wei ; Zhou, Wei ; Zimmermann, Martina E. ; Zoledziewska, Magdalena ; 't Hart, Leen M. ; Adair, Linda S. ; Adams, Hieab H. H. ; Aguilar-Salinas, Carlos A. ; Al-Mulla, Fahd ; Arnett, Donna K. ; Asselbergs, Folkert W. ; Åsvold, Bjørn Olav ; Attia, John ; Banas, Bernhard ; Bandinelli, Stefania ; Beilin, Lawrence J. ; Bennett, David A. ; Bergler, Tobias ; Bharadwaj, Dwaipayan ; Biino, Ginevra ; Boerwinkle, Eric ; Böger, Carsten A. ; Borja, Judith B. ; Bouchard, Claude ; Bowden, Donald W. ; Brandslund, Ivan ; Brumpton, Ben ; Buring, Julie E. ; Caulfield, Mark J. ; Chambers, John C. ; Chandak, Giriraj R. ; Chanock, Stephen J. ; Chaturvedi, Nish ; Ida Chen, Yii-Der ; Chen, Zhengming ; Cheng, Ching-Yu ; Cho, Yoon Shin ; Christensen, Kaare ; Christophersen, Ingrid E. ; Ciullo, Marina ; Cole, John W. ; Collins, Francis S. ; Concas, Maria Pina ; Cooper, Richard S. ; Cruz, Miguel ; Cucca, Francesco ; Cutler, Michael J. ; Damrauer, Scott M. ; Dantoft, Thomas M. ; de Borst, Gert J. ; de Geus, Eco J. C. ; de Groot, Lisette C. P. G. M. ; De Jager, Philip L. ; de Kleijn, Dominique P. V. ; Janaka de Silva, H. ; Dedoussis, George V. ; den Hollander, Anneke I. ; Du, Shufa ; Easton, Douglas F. ; Eckardt, Kai-Uwe ; Elders, Petra J. M. ; Heather Eliassen, A. ; Ellinor, Patrick T. ; Elmståhl, Sölve ; Erdmann, Jeanette ; Evans, Michele K. ; Fatkin, Diane ; Feenstra, Bjarke ; Feitosa, Mary F. ; Ferrucci, Luigi ; Florez, Jose C. ; Ford, Ian ; Fornage, Myriam ; Franke, Andre ; Franks, Paul W. ; Freedman, Barry I. ; Gieger, Christian ; Girotto, Giorgia ; Golightly, Yvonne M. ; Gonzalez-Villalpando, Clicerio ; Gordon-Larsen, Penny ; Grallert, Harald ; Grant, Struan F. A. ; Grarup, Niels ; Griffiths, Lyn ; Gudnason, Vilmundur ; Haiman, Christopher ; Hakonarson, Hakon ; Hansen, Torben ; Hartman, Catharina A. ; Hattersley, Andrew T. ; Hayward, Caroline ; Heid, Iris M. ; Heng, Chew-Kiat ; Hengstenberg, Christian ; Herzig, Karl-Heinz ; Hewitt, Alex W. ; Hishigaki, Haretsugu ; Hougaard, David M. ; Hoyng, Carel B. ; Huang, Paul L. ; Huang, Wei ; Huang, Wen-Yi ; Huffman, Jennifer E. ; Hunt, Steven C. ; Hutri, Nina ; Hveem, Kristian ; Hyppönen, Elina ; Iacono, William G. ; Ichihara, Sahoko ; Arfan Ikram, M. ; Isasi, Carmen R. ; Jarvelin, Marjo-Riitta ; Jin, Zi-Bing ; Jöckel, Karl-Heinz ; Jonas, Jost B. ; Joshi, Peter K. ; Jousilahti, Pekka ; Wouter Jukema, J. ; Kähönen, Mika ; Kamatani, Yoichiro ; Kang, Kui Dong ; Kaprio, Jaakko ; Kardia, Sharon L. R. ; Karpe, Fredrik ; Kato, Norihiro ; Kavousi, Maryam ; Kee, Frank ; Kessler, Thorsten ; Khera, Amit V. ; Khor, Chiea Chuen ; Kiemeney, Lambertus A. L. M. ; Kim, Bong-Jo ; Kim, Eung Kweon ; Kim, Hyung-Lae ; Kirchhof, Paulus ; Kivimaki, Mika ; Koh, Woon-Puay ; Koistinen, Heikki A. ; Kokkinos, Alexander ; Kooner, Jaspal S. ; Kooperberg, Charles ; Kovacs, Peter ; Kraaijeveld, Adriaan ; Kraft, Peter ; Krauss, Ronald M. ; Kumari, Meena ; Kutalik, Zoltan ; Laakso, Markku ; Lange, Leslie A. ; Langenberg, Claudia ; Launer, Lenore J. ; Lee, Hyejin ; Lee, Nanette R. ; Lehtimäki, Terho ; Lemaitre, Rozenn N. ; Li, Huaixing ; Li, Liming ; Lieb, Wolfgang ; Lin, Xu ; Lind, Lars ; Linneberg, Allan ; Liu, Ching-Ti ; Liu, Jianjun ; Loeffler, Markus ; London, Barry ; Lu, Fan ; Lubitz, Steven A. ; Mackey, David A. ; Magnusson, Patrik K. E. ; Manson, JoAnn E. ; Marcus, Gregory M. ; Vidal, Pedro Marques ; Martin, Nicholas G. ; März, Winfried ; Matsuda, Fumihiko ; McCarthy, Mark I. ; McGarrah, Robert W. ; McGue, Matt ; McKnight, Amy Jayne ; Medland, Sarah E. ; Mellström, Dan ; Metspalu, Andres ; Mitchell, Braxton D. ; Mitchell, Paul ; Mook-Kanamori, Dennis O. ; Mori, Trevor A. ; Morris, Andrew D. ; Mucci, Lorelei A. ; Munroe, Patricia B. ; Nalls, Mike A. ; Nazarian, Saman ; Nelson, Amanda E. ; Neville, Matt J. ; Newton-Cheh, Christopher ; Nielsen, Christopher S. ; Niinikoski, Harri ; Nikus, Kjell ; Nöthen, Markus M. ; Ogunniyi, Adesola ; Ohlsson, Claes ; Oldehinkel, Albertine J. ; Orozco, Lorena ; Pahkala, Katja ; Pajukanta, Päivi ; Palmer, Colin N. A. ; Parra, Esteban J. ; Pattaro, Cristian ; Pedersen, Oluf ; Pennell, Craig E. ; Penninx, Brenda W. J. H. ; Perusse, Louis ; Peters, Annette ; Peyser, Patricia A. ; Porteous, David J. ; Posthuma, Danielle ; Power, Chris ; Pramstaller, Peter P. ; Province, Michael A. ; Psaty, Bruce M. ; Qi, Qibin ; Qu, Jia ; Rader, Daniel J. ; Raitakari, Olli T. ; Rallidis, Loukianos S. ; Rao, Dabeeru C. ; Redline, Susan ; Reilly, Dermot F. ; Reiner, Alexander P. ; Rhee, Sang Youl ; Ridker, Paul M. ; Rienstra, Michiel ; Ripatti, Samuli ; Ritchie, Marylyn D. ; Rivadeneira, Fernando ; Roden, Dan M. ; Rosendaal, Frits R. ; Rotter, Jerome I. ; Rudan, Igor ; Rutters, Femke ; Ryu, Seungho ; Sabanayagam, Charumathi ; Salako, Babatunde ; Saleheen, Danish ; Salomaa, Veikko ; Samani, Nilesh J. ; Sanghera, Dharambir K. ; Sattar, Naveed ; Schmidt, Börge ; Schmidt, Helena ; Schmidt, Reinhold ; Schulze, Matthias B. ; Schunkert, Heribert ; Scott, Laura J. ; Scott, Rodney J. ; Sever, Peter ; Sheu, Wayne H. H. ; Benjamin Shoemaker, M. ; Shu, Xiao-Ou ; Simonsick, Eleanor M. ; Sims, Mario ; Singleton, Andrew B. ; Sinner, Moritz F. ; Gustav Smith, J. ; Snieder, Harold ; Spector, Tim D. ; Spedicati, Beatrice ; Stampfer, Meir J. ; Stark, Klaus J. ; Strachan, David P. ; Tabara, Yasuharu ; Shyong Tai, E. ; Tang, Hua ; Tardif, Jean-Claude ; Thanaraj, Thangavel A. ; Tönjes, Anke ; Tuomi, Tiinamaija ; Tuomilehto, Jaakko ; Tusié-Luna, Maria-Teresa ; van Dam, Rob M. ; van der Harst, Pim ; Van der Velde, Nathalie ; van Duijn, Cornelia M. ; van Schoor, Natasja M. ; Vitart, Veronique ; Vohl, Marie-Claude ; Völker, Uwe ; Vollenweider, Peter ; Völzke, Henry ; Vrieze, Scott ; Wacher-Rodarte, Niels H. ; Walker, Mark ; Wander, Gurpreet S. ; Wareham, Nicholas J. ; Watanabe, Richard M. ; Watkins, Hugh ; Weir, David R. ; Werge, Thomas M. ; Widen, Elisabeth ; Willemsen, Gonneke ; Willett, Walter C. ; Wilson, James F. ; Wilson, Peter W. F. ; Wong, Tien Y. ; Woo, Jeong-Taek ; Wright, Alan F. ; Xu, Huichun ; Yajnik, Chittaranjan S. ; Yang, Jian ; Yokota, Mitsuhiro ; Yuan, Jian-Min ; Zeggini, Eleftheria ; Zemel, Babette S. ; Zheng, Wei ; Zhu, Xiaofeng ; Carola Zillikens, M. ; Zonderman, Alan B. ; Zwart, John-Anker ; Abecasis, Goncalo R. ; Assimes, Themistocles L. ; Auton, Adam ; Boehnke, Michael ; Chasman, Daniel I. ; Esko, Tõnu ; Stefansson, Kari ; Lettre, Guillaume ; Lindgren, Cecilia M. ; Ng, Maggie C. Y. ; O'Donnell, Christopher J. ; Thorsteinsdottir, Unnur ; Visscher, Peter M. ; Walters, Robin G. ; Winkler, Thomas W. ; Wood, Andrew R. ; Deloukas, Panos ; Frayling, Timothy M. ; Justice, Anne E. ; Kilpeläinen, Tuomas O. ; Locke, Adam E. ; Mohlke, Karen L. ; North, Kari E. ; Okada, Yukinori ; Willer, Cristen J. ; Young, Kristin L. ; Fatumo, Segun ; McCaffery, Jeanne M. ; Timpson, Nicholas J. ; Hirschhorn, Joel N. ; Sun, Yan V. ; Berndt, Sonja I. ; Loos, Ruth J. F.
• Corporate Authors:
  23andMe Research Team ; DiscovEHR (DiscovEHR and MyCode Community Health Initiative) ; eMERGE (Electronic Medical Records and Genomics Network) ; GPC-UGR ; The PRACTICAL Consortium ; Understanding Society Scientific Group ; VA Million Veteran Program
• Description:
  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.
• Content Notes:
  Author manuscript
• Subjects:
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Middle Aged
  • Young Adult
  • Adiposity
  More +
• Keywords:
  • Obesity
  • Predictive markers
• Source:
  Nature Medicine, 2025, v. 31, no. 9
• DOI:
  https://doi.org/10.1038/s41591-025-03827-z
• ISSN:
  1078-8956 ; 1546-170X
• Pubmed ID:
  40691366
• Pubmed Central ID:
  PMC12443623
• Document Type:
  Text
• Funding:
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N01 HC095164/HL/NHLBI NIH HHSUnited States/ ; R37 DA005147/DA/NIDA NIH HHSUnited States/ ; UL1 TR001881/TR/NCATS NIH HHSUnited States/ ; HHSN268201700003I/HL/NHLBI NIH HHSUnited States/ ; R01 HG010297/HG/NHGRI NIH HHSUnited States/ ; HHSN268201800006I/HL/NHLBI NIH HHSUnited States/ ; U01 HL054495/HL/NHLBI NIH HHSUnited States/ ; U01 CA164973/CA/NCI NIH HHSUnited States/ ; R37 CA054281/CA/NCI NIH HHSUnited States/ ; 75N92021D00004/WH/WHI NIH HHSUnited States/ ; N01 HC065237/HL/NHLBI NIH HHSUnited States/ ; UM1 CA182883/CA/NCI NIH HHSUnited States/ ; HHSN271201200022C/DA/NIDA NIH HHSUnited States/ ; HHSN268201200008I/HL/NHLBI NIH HHSUnited States/ ; N01 HC085081/HL/NHLBI NIH HHSUnited States/ ; R01 DK078150/DK/NIDDK NIH HHSUnited States/ ; K07 AG061256/AG/NIA NIH HHSUnited States/ ; R01 CA141298/CA/NCI NIH HHSUnited States/ ; U01 HL054473/HL/NHLBI NIH HHSUnited States/ ; R01 DA044283/DA/NIDA NIH HHSUnited States/ ; U01 HG008701/HG/NHGRI NIH HHSUnited States/ ; UM1 CA182876/CA/NCI NIH HHSUnited States/ ; R37 AA012502/AA/NIAAA NIH HHSUnited States/ ; R01 DK122503/DK/NIDDK NIH HHSUnited States/ ; N01 HC095160/HL/NHLBI NIH HHSUnited States/ ; R01 AA013320/AA/NIAAA NIH HHSUnited States/ ; K08 HG010155/HG/NHGRI NIH HHSUnited States/ ; K01 HL135405/HL/NHLBI NIH HHSUnited States/ ; P30 AR072580/AR/NIAMS NIH HHSUnited States/ ; R01 AG056477/AG/NIA NIH HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  3151-3168 (75 pdf pages)
• Volume:
  31
• Issue:
  9
• Download URL:
  https://stacks.cdc.gov/view/cdc/262117/cdc_262117_DS1.pdf
• File Type:
  [PDF - 3.54 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:b36597ff046090c381100642e7d63a8d594efa166a883f7a5bd52d96443b946f13ccdfe0b8b097bafc0e81356780910d48aa9a05f7e2f47a7fc5786f3d8b2721