Start Over

Polygenic prediction of weight and obesity trajectories from birth to adulthood

Authors :: Mark Chaffin
Krishna G. Aragam
Nicholas J. Timpson
Ozlem Senol-Cosar
Alexander G. Bick
Matthew S. Lebo
Mary E. Haas
Sohail Zahid
Lee M. Kaplan
Heather Mason-Suares
Sekar Kathiresan
Marina T. DiStefano
Amit Khera
Kaitlin H Wade
Rui Xia
George Davey Smith
Myriam Fornage
Eric S. Lander
Joseph Brancale
Massachusetts Institute of Technology. Department of Biology
Source :: Khera, A V, Chaffin, M, Wade, K H, Zahid, S, Brancale, J, Xia, R, Distefano, M, Senol-Cosar, O, Haas, M E, Bick, A, Aragam, K G, Lander, E S, Smith, G D, Mason-Suares, H, Fornage, M, Lebo, M, Timpson, N J, Kaplan, L M & Kathiresan, S 2019, ' Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood ', Cell, vol. 177, no. 3, pp. 587-596.e9 . https://doi.org/10.1016/j.cell.2019.03.028, PMC
Publication Year :: 2019
Abstract: 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)

Details

Language :: English
Database :: OpenAIRE
Journal :: Khera, A V, Chaffin, M, Wade, K H, Zahid, S, Brancale, J, Xia, R, Distefano, M, Senol-Cosar, O, Haas, M E, Bick, A, Aragam, K G, Lander, E S, Smith, G D, Mason-Suares, H, Fornage, M, Lebo, M, Timpson, N J, Kaplan, L M & Kathiresan, S 2019, ' Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood ', Cell, vol. 177, no. 3, pp. 587-596.e9 . https://doi.org/10.1016/j.cell.2019.03.028, PMC
Accession number :: edsair.doi.dedup.....818a8eba2d6b4ea4b9dc356086cec7d8
Full Text :: https://doi.org/10.1016/j.cell.2019.03.028