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.
Authors
Smit Smit, Wade Wade, Hui Hui, Arias Arias, Yin Yin, Christiansen Christiansen, Yengo Yengo, Preuss Preuss, Nakabuye Nakabuye, Rocheleau Rocheleau, Graham Graham, Buchanan Buchanan, Chittoor Chittoor, Graff Graff, Guindo-Martínez Guindo-Martínez, Lu Lu, Marouli Marouli, Sakaue Sakaue, Spracklen Spracklen, Vedantam Vedantam, Wilson Wilson, Chen Chen, Ferreira Ferreira, Ji Ji, Karaderi Karaderi, Lüll Lüll, Machado Machado, Malden Malden, Medina-Gomez Medina-Gomez, Moore Moore, Rüeger Rüeger, Akiyama Akiyama, Allison Allison, Alvarez Alvarez, Andersen Andersen, Appadurai Appadurai, Arbeeva Arbeeva, Bartell Bartell, Bhaskar Bhaskar, Bielak Bielak, Bis Bis, Bollepalli Bollepalli, Bork-Jensen Bork-Jensen, Bradfield Bradfield, Bradford Bradford, Brandl Brandl, Braund Braund, Brody Brody, Broeckel Broeckel, Burgdorf Burgdorf, Cade Cade, Cai Cai, Camarda Camarda, Campbell Campbell, Cañadas-Garre Cañadas-Garre, Chai Chai, Chesi Chesi, Choi Choi, Christofidou Christofidou, Couture Couture, Cuellar-Partida Cuellar-Partida, Danning Danning, Degenhardt Degenhardt, Delgado Delgado, Delitala Delitala, Demirkan Demirkan, Deng Deng, Dietl Dietl, Dimitriou Dimitriou, Dimitrov Dimitrov, Dorajoo Dorajoo, Eichelmann Eichelmann, Eliasen Eliasen, Engmann Engmann, Erdos Erdos, Fairhurst-Hunter Fairhurst-Hunter, Farmaki Farmaki, Faul Faul, Fernandez-Lopez Fernandez-Lopez, Forer Forer, Frank Frank, Freitag-Wolf Freitag-Wolf, Fritsche Fritsche, Fuchsberger Fuchsberger, Galesloot Galesloot, Gao Gao, Geller Geller, Giannakopoulou Giannakopoulou, Giulianini Giulianini, Gjesing Gjesing, Goel Goel, Gordon Gordon, Gorski Gorski, Grove Grove, Guo Guo, Gustafsson Gustafsson, Haessler Haessler, Hansen Hansen, Havulinna Havulinna, Haworth Haworth, Heard-Costa Heard-Costa, Hemerich Hemerich, Highland Highland, Hindy Hindy, Ho Ho, Hofer Hofer, Holliday Holliday, Horn Horn, Hornsby Hornsby, Hottenga Hottenga, Huang Huang, Huang Huang, Huerta-Chagoya Huerta-Chagoya, Huo Huo, Hwang Hwang, Hwu Hwu, Iha Iha, Ikeda Ikeda, Isono Isono, Jackson Jackson, Jansen Jansen, Jiang Jiang, Johansson Johansson, Jonsson Jonsson, Jørgensen Jørgensen, Kalafati Kalafati, Kanai Kanai, Kanoni Kanoni, Kårhus Kårhus, Kasturiratne Kasturiratne, Katsuya Katsuya, Kawaguchi Kawaguchi, Kember Kember, Kentistou Kentistou, Kim Kim, Kim Kim, Kim Kim, Kleber Kleber, Knol Knol, Kurbasic Kurbasic, Lauzon Lauzon, Le Le, Lea Lea, Lee Lee, Lee Lee, Leonard Leonard, Li Li, Li Li, Li Li, Li Li, Liang Liang, Lin Lin, Lin Lin, Liu Liu, Liu Liu, Lo Lo, Long Long, Lores-Motta Lores-Motta, Luan Luan, Lyssenko Lyssenko, Lyytikäinen Lyytikäinen, Mahajan Mahajan, Malik Malik, Mamakou Mamakou, Mangino Mangino, Manichaikul Manichaikul, Marten Marten, Mattheisen Mattheisen, McDaid McDaid, Mei Mei, Meiselbach Meiselbach, Melendez Melendez, Milaneschi Milaneschi, Miller Miller, Millwood Millwood, Mishra Mishra, Mitchell Mitchell, Møllehave Møllehave, Mononen Mononen, Mucha Mucha, Munz Munz, Mykkänen Mykkänen, Nakatochi Nakatochi, Nardone Nardone, Nelson Nelson, Nethander Nethander, Nho Nho, Nielsen Nielsen, Nolte Nolte, Nongmaithem Nongmaithem, Noordam Noordam, Ntalla Ntalla, Nutile Nutile, Pandit Pandit, Pauper Pauper, Petersen Petersen, Petersen Petersen, Piluso Piluso, Polašek Polašek, Poveda Poveda, Pyarajan Pyarajan, Raffield Raffield, Rakugi Rakugi, Ramirez Ramirez, Rasheed Rasheed, Raven Raven, Rayner Rayner, Riveros Riveros, Rohde Rohde, Ruggiero Ruggiero, Ruotsalainen Ruotsalainen, Ryan Ryan, Sabater-Lleal Sabater-Lleal, Santin Santin, Saxena Saxena, Scholz Scholz, Shen Shen, Shi Shi, Shin Shin, Sidore Sidore, Sidorenko Sidorenko, Sim Sim, Slieker Slieker, Smith Smith, Smith Smith, Smyth Smyth, Southam Southam, Steinthorsdottir Steinthorsdottir, Sun Sun, Takeuchi Takeuchi, Taylor Taylor, Tayo Tayo, Tcheandjieu Tcheandjieu, Terzikhan Terzikhan, Tesolin Tesolin, Teumer Teumer, Theusch Theusch, Thompson Thompson, Thorleifsson Thorleifsson, Timmers Timmers, Trompet Trompet, Turman Turman, Vaccargiu Vaccargiu, van der Laan van der Laan, van der Most van der Most, van Klinken van Klinken, van Setten van Setten, Verma Verma, Verweij Verweij, Veturi Veturi, Wang Wang, Wang Wang, Wang Wang, Wang Wang, Wang Wang, Wang Wang, Warren Warren, Bin Wei Bin Wei, Wen Wen, Wheeler Wheeler, Wickremasinghe Wickremasinghe, Wielscher Wielscher, Winsvold Winsvold, Wong Wong, Wuttke Wuttke, Xia Xia, Yamamoto Yamamoto, Yang Yang, Yao Yao, Young Young, Yousri Yousri, Yu Yu, Zeng Zeng, Zhang Zhang, Zhang Zhang, Zhao Zhao, Zhao Zhao, Zhou Zhou, Zimmermann Zimmermann, Zoledziewska Zoledziewska, 't Hart 't Hart, Adair Adair, Adams Adams, Aguilar-Salinas Aguilar-Salinas, Al-Mulla Al-Mulla, Arnett Arnett, Asselbergs Asselbergs, Åsvold Åsvold, Attia Attia, Banas Banas, Bandinelli Bandinelli, Beilin Beilin, Bennett Bennett, Bergler Bergler, Bharadwaj Bharadwaj, Biino Biino, Boerwinkle Boerwinkle, Böger Böger, Borja Borja, Bouchard Bouchard, Bowden Bowden, Brandslund Brandslund, Brumpton Brumpton, Buring 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Laakso Laakso, Lange Lange, Langenberg Langenberg, Launer Launer, Lee Lee, Lee Lee, Lehtimäki Lehtimäki, Lemaitre Lemaitre, Li Li, Li Li, Lieb Lieb, Lin Lin, Lind Lind, Linneberg Linneberg, Liu Liu, Liu Liu, Loeffler Loeffler, London London, Lu Lu, Lubitz Lubitz, Mackey Mackey, Magnusson Magnusson, Manson Manson, Marcus Marcus, Marques Vidal Marques Vidal, Martin Martin, März März, Matsuda Matsuda, McCarthy McCarthy, McGarrah McGarrah, McGue McGue, McKnight McKnight, Medland Medland, Mellström Mellström, Metspalu Metspalu, Mitchell Mitchell, Mitchell Mitchell, Mook-Kanamori Mook-Kanamori, Mori Mori, Morris Morris, Mucci Mucci, Munroe Munroe, Nalls Nalls, Nazarian Nazarian, Nelson Nelson, Neville Neville, Newton-Cheh Newton-Cheh, Nielsen Nielsen, Niinikoski Niinikoski, Nikus Nikus, Nöthen Nöthen, Ogunniyi Ogunniyi, Ohlsson Ohlsson, Oldehinkel Oldehinkel, Orozco Orozco, Pahkala Pahkala, Pajukanta Pajukanta, Palmer Palmer, Parra Parra, Pattaro Pattaro, Pedersen Pedersen, Pennell Pennell, Penninx Penninx, Perusse Perusse, Peters Peters, Peyser Peyser, Porteous Porteous, Posthuma Posthuma, Power Power, Pramstaller Pramstaller, Province Province, Psaty Psaty, Qi Qi, Qu Qu, Rader Rader, Raitakari Raitakari, Rallidis Rallidis, Rao Rao, Redline Redline, Reilly Reilly, Reiner Reiner, Rhee Rhee, Ridker Ridker, Rienstra Rienstra, Ripatti Ripatti, Ritchie Ritchie, Rivadeneira Rivadeneira, Roden Roden, Rosendaal Rosendaal, Rotter Rotter, Rudan Rudan, Rutters Rutters, Ryu Ryu, Sabanayagam Sabanayagam, Salako Salako, Saleheen Saleheen, Salomaa Salomaa, Samani Samani, Sanghera Sanghera, Sattar Sattar, Schmidt Schmidt, Schmidt Schmidt, Schmidt Schmidt, Schulze Schulze, Schunkert Schunkert, Scott Scott, Scott Scott, Sever Sever, Sheu Sheu, Shoemaker Shoemaker, Shu Shu, Simonsick Simonsick, Sims Sims, Singleton Singleton, Sinner Sinner, Smith Smith, Snieder Snieder, Spector Spector, Spedicati Spedicati, Stampfer Stampfer, Stark Stark, Strachan Strachan, Tabara Tabara, Tai Tai, Tang 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