Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood
Name
nihms-1535553.pdf
Description
Accepted version
Size
1.58 MB
Format
Adobe PDF
Checksum (MD5)
96eccf15cd1faf3fe22308ec307f4d0b
Author(s)
Khera, Amit V.
Chaffin, Mark
Wade, Kaitlin H.
Zahid, Sohail
Brancale, Joseph
Xia, Rui
Distefano, Marina
Senol-Cosar, Ozlem
Haas, Mary E.
Bick, Alexander
Date Issued
April 2019
Journal
Cell
Publisher
Elsevier BV
Citation
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)
Version
Author's final manuscript
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)
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2019.03.028
