Projects per year
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 impact 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 >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 difference in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by age 18 years. This new approach to quantify inherited susceptibility to obesity using affords new opportunities for clinical prevention and mechanistic assessment.
Original language | English |
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Pages (from-to) | 587-596.e9 |
Number of pages | 20 |
Journal | Cell |
Volume | 177 |
Issue number | 3 |
Early online date | 18 Apr 2019 |
DOIs | |
Publication status | Published - 18 Apr 2019 |
Research Groups and Themes
- ALSPAC
Keywords
- polygenic score
- human genetics
- genomic medicine
- genetic risk prediction
- melanocortin 4 receptor
- severe obesity
- weight
- body mass index
- UK Biobank
Fingerprint
Dive into the research topics of 'Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood'. Together they form a unique fingerprint.Projects
- 2 Finished
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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research
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NIHR BRC Translational Population Health
Davey Smith, G. (Principal Investigator)
1/04/17 → 31/03/22
Project: Research, Parent
Profiles
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Professor George Davey Smith
- MRC Integrative Epidemiology Unit
- Bristol Medical School (PHS) - Professor of Clinical Epidemiology
Person: Academic , Member, Group lead
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Professor Nicholas John Timpson
- Bristol Medical School (PHS) - Professor of Genetic Epidemiology
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
- Cancer
Person: Academic , Member