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GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI
| File | Description | Size | Format | |
|---|---|---|---|---|
 EAP_Supplementary_Information_ScienceAdvances_ACCEPTED.docx | Supporting information | 11.17 MB | Microsoft Word | View/Open |
 GWASOnLongitudinalGrowthTraits.pdf | Published version | 1.86 MB | Adobe PDF | View/Open |
| Title: | GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI |
| Authors: | Alves, AC De Silva, NMG Karhunen, V Sovio, U Das, S Rob Taal, H Warrington, NM Lewin, AM Kaakinen, M Cousminer, DL Thiering, E Timpson, NJ Bond, TA Lowry, E Brown, CD Estivill, X Lindi, V Bradfield, JP Geller, F Speed, D Coin, LJM Loh, M Barton, SJ Beilin, LJ Bisgaard, H Bønnelykke, K Alili, R Hatoum, IJ Schramm, K Cartwright, R Charles, MA Salerno, V Clément, K Claringbould, AAJ Van Duijn, CM Moltchanova, E Eriksson, JG Elks, C Feenstra, B Flexeder, C Franks, S Frayling, TM Freathy, RM Elliott, P Widén, E Hakonarson, H Hattersley, AT Rodriguez, A Banterle, M Heinrich, J Heude, B Holloway, JW Hofman, A Hyppönen, E Inskip, H Kaplan, LM Hedman, AK Läärä, E Prokisch, H Grallert, H Lakka, TA Lawlor, DA Melbye, M Ahluwalia, TS Marinelli, M Millwood, IY Palmer, LJ Pennell, CE Perry, JR Ring, SM Savolainen, MJ Rivadeneira, F Standl, M Sunyer, J Tiesler, CMT Uitterlinden, AG Schierding, W Sullivan, OM Prokopenko, I Herzig, KH Smith, GD O'Reilly, P Felix, JF Buxton, JL Blakemore, AIF Ong, KK Jaddoe, VWV Grant, SFA Sebert, S McCarthy, MI Järvelin, MR |
| Item Type: | Journal Article |
| Abstract: | Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here we combine genome-wide association studies with modelling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score and co-localization analyses to determine how developmental timings, molecular pathways and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult BMI, with variants associated with adult BMI acting as early as 4-6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies. |
| Issue Date: | 4-Sep-2019 |
| Date of Acceptance: | 6-Aug-2019 |
| URI: | http://hdl.handle.net/10044/1/71531 |
| DOI: | 10.1126/sciadv.aaw3095 |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Journal / Book Title: | Science Advances |
| Volume: | 5 |
| Issue: | 9 |
| Copyright Statement: | Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). This is an open-access article distributed under the terms of the Creative Commons Attribution license ( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Sponsor/Funder: | Medical Research Council (MRC) Medical Research Council (MRC) |
| Funder's Grant Number: | MR/L01341X/1 G0802782 |
| Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics BODY-MASS INDEX GENOME-WIDE ASSOCIATION BLOOD-PRESSURE EARLY-LIFE METABOLIC RISK BIRTH COHORT FTO GENE ADIPOSITY OBESITY AGE |
| Publication Status: | Published |
| Article Number: | eaaw3095 |
| Appears in Collections: | School of Public Health |