Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood
Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/125217 |
| _version_ | 1811091232903921664 |
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| author | Khera, Amit V. Chaffin, Mark Wade, Kaitlin H. Zahid, Sohail Brancale, Joseph Xia, Rui Distefano, Marina Senol-Cosar, Ozlem Haas, Mary E. Bick, Alexander Aragam, Krishna G. Lander, Eric Steven Smith, George Davey Mason-Suares, Heather Fornage, Myriam Lebo, Matthew Timpson, Nicholas J. Kaplan, Lee M. Kathiresan, Sekar |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Khera, Amit V. Chaffin, Mark Wade, Kaitlin H. Zahid, Sohail Brancale, Joseph Xia, Rui Distefano, Marina Senol-Cosar, Ozlem Haas, Mary E. Bick, Alexander Aragam, Krishna G. Lander, Eric Steven Smith, George Davey Mason-Suares, Heather Fornage, Myriam Lebo, Matthew Timpson, Nicholas J. Kaplan, Lee M. Kathiresan, Sekar |
| author_sort | Khera, Amit V. |
| collection | MIT |
| description | Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment. © 2019 Author(s) |
| first_indexed | 2024-09-23T14:59:04Z |
| format | Article |
| id | mit-1721.1/125217 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:59:04Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1252172022-10-01T23:46:26Z Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood Khera, Amit V. Chaffin, Mark Wade, Kaitlin H. Zahid, Sohail Brancale, Joseph Xia, Rui Distefano, Marina Senol-Cosar, Ozlem Haas, Mary E. Bick, Alexander Aragam, Krishna G. Lander, Eric Steven Smith, George Davey Mason-Suares, Heather Fornage, Myriam Lebo, Matthew Timpson, Nicholas J. Kaplan, Lee M. Kathiresan, Sekar Massachusetts Institute of Technology. Department of Biology Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment. © 2019 Author(s) National Human Genome Research Institute (1K08HG0101) Wellcome Trust (202802/Z/16/Z) University of Bristol NIHR Biomedical Research Centre (S- BRC-1215-20011) National Human Genome Research Institute (HG008895) National Heart, Lung, and Blood Institute (NHLBI) HHSN268201300025C National Heart, Lung, and Blood Institute (NHLBI) HHSN268201300026C National Heart, Lung, and Blood Institute (NHLBI) HHSN268201300027C National Heart, Lung, and Blood Institute (NHLBI) HHSN268201300028C National Heart, Lung, and Blood Institute (NHLBI) HHSN268201300029C National Heart, Lung, and Blood Institute (NHLBI) HHSN268200900041C National Institute on Aging (AG0005) NHLBI (AG0005) National Human Genome Research Institute (U01-HG004729) National Human Genome Research Institute (U01-HG04424) National Human Genome Research Institute (U01-HG004446) Wellcome (102215/2/13/2) 2020-05-13T17:50:30Z 2020-05-13T17:50:30Z 2019-04 2020-05-11T15:23:59Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 https://hdl.handle.net/1721.1/125217 Khera, Amit V., et al. "Polygenic prediction of weight and obesity trajectories from birth to adulthood." Cell 177:3 (April 2019): 587–596 © 2019 Author(s) en 10.1016/J.CELL.2019.03.028 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Khera, Amit V. Chaffin, Mark Wade, Kaitlin H. Zahid, Sohail Brancale, Joseph Xia, Rui Distefano, Marina Senol-Cosar, Ozlem Haas, Mary E. Bick, Alexander Aragam, Krishna G. Lander, Eric Steven Smith, George Davey Mason-Suares, Heather Fornage, Myriam Lebo, Matthew Timpson, Nicholas J. Kaplan, Lee M. Kathiresan, Sekar Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood |
| title | Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood |
| title_full | Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood |
| title_fullStr | Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood |
| title_full_unstemmed | Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood |
| title_short | Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood |
| title_sort | polygenic prediction of weight and obesity trajectories from birth to adulthood |
| url | https://hdl.handle.net/1721.1/125217 |
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