TY - JOUR
T1 - Dietary Intake, FTO Genetic Variants, and Adiposity
T2 - A Combined Analysis of Over 16,000 Children and Adolescents
AU - Qi, Qibin
AU - Downer, MK
AU - Kilpeläinen, TO
AU - Taal, HR
AU - Barton, SJ
AU - Ntalla, I
AU - Standl, M
AU - Boraska, V
AU - Huikari, V
AU - Kiefte-de, Jong JC
AU - Körner, A
AU - Lakka, TA
AU - Liu, G
AU - Magnusson, J
AU - Okuda, M
AU - Raitakari, O
AU - Richmond, R
AU - Scott, RA
AU - Bailey , MES
AU - Scheuermann, K
AU - Holloway, JW
AU - Inskip, H
AU - Isasi, CR
AU - Mossavar-Rahmani, Y
AU - Jaddoe, VWV
AU - Laitinen, J
AU - Lindi, V
AU - Melén, E
AU - PITSILADIS, Yannis
AU - Pitkänen, N
AU - Snieder, H
AU - Heinrich, J
AU - Timpson, NJ
AU - Wang, Tao
AU - Yuji, H
AU - Zeggini, E
AU - Dedoussis, GV
AU - Kaplan, RC
AU - Wylie-Rosett, J
AU - Loos, RJF
AU - Hu, FB
AU - Qi, L
N1 - There was no specific funding for this project. Funding sources for the individual authors and for the studies included in the analysis are listed as follows. The ALSPAC study was supported by Medical Research Council grant MC_UU_12013/1-9. The APEX project was supported by National Institutes of Health (NIH) grant HL64972. The authors thank Haidong Zhu, Bernard Gutin, Inger S. Stallmann-Jorgensen, and Yanbin Dong (Georgia Prevention Center, Georgia Regents University, Augusta, GA) for their contributions to conducting the study and data collection. The BAMSE study was funded by The Swedish Research Council, The Swedish Heart-Lung Foundation, Stockholm County Council (ALF), and the SFO Epidemiology Program at Karolinska Institutet. The GENDAI study was partially supported by a research grant from Coca-Cola Hellas. The GENR study is being conducted by the Erasmus Medical Center and Erasmus University Rotterdam in close collaboration with the Municipal Health Service Rotterdam area, Rotterdam, and the Stichting Trombosedienst en Artsenlaboratorium Rijnmond, Rotterdam. The authors thank the children and their parents, general practitioners, hospitals, midwives, and pharmacies in Rotterdam for their contribution. The generation and management of GWAS genotype data for the Generation R Study were performed at the Genetic Laboratory of the Department of Internal Medicine, Erasmus Medical Center, the Netherlands. The authors thank Karol Estrada, Dr. Tobias A. Knoch, Anis Abuseiris, Luc V. de Zeeuw, and Rob de Graaf for their help in creating GRIMP, BigGRID, MediGRID, and Services@MediGRID/D-Grid (funded by the German Bundesministerium fuer Forschung und Technology, grants 01 AK 803 A-H, 01 IG 07015 G) for access to their grid computing resources. The authors also thank Mila Jhamai, Manoushka Ganesh, Pascal Arp, Marijn Verkerk, Lizbeth Herrera, and Marjolein Peters for their help in the creation, management, and quality control of the GWAS database. Also, the authors thank Karol Estrada and Carolina Medina-Gomez for their support in the creation and analysis of imputed data. In addition, the authors thank Henriette Moll for her support in calculating the dietary intakes. The Generation R Study receives financial support from the Erasmus University Medical Center, Rotterdam, and The Netherlands Organisation for Health Research and Development (ZonMw). V.W.V.J. received an additional grant from ZonMw (ZonMw VIDI: 016.136.361). Additional support was provided by a grant from the Dutch Kidney Foundation (C08.2251). The GINI study team thanks the following: Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Epidemiology I, Munich (J. Heinrich, H.E. Wichmann, S. Sausenthaler, C.-M. Chen, E. Thiering, C.M.T. Tiesler, M. Schnappinger, and P. Rzehak); Department of Pediatrics, Marien-Hospital, Wesel (D. Berdel, A. von Berg, C. Beckmann, and I. Gross); Department of Pediatrics, Ludwig Maximilians University, Munich (S. Koletzko, D. Reinhardt, and S. Krauss-Etschmann); Department of Pediatrics, Technical University, Munich (C.P. Bauer, I. Brockow, A. Grübl, and U. Hoffmann); IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf (U. Krämer, E. Link, and C. Cramer); and the Centre of Allergy & Environment, Technical University, Munich (H. Behrendt). The LISA study team wishes to acknowledge the following: Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg (J. Heinrich, H.E. Wichmann, S. Sausenthaler, C.-M. Chen, and C.M.T. Tiesler); University of Leipzig, Department of Pediatrics (M. Borte); Department of Environmental Medicine and Hygiene (O. Herbarth); Department of Pediatrics, Marien Hospital, Wesel (A. von Berg); Bad Honnef (B. Schaaf); UFZ-Centre for Environmental Research Leipzig-Halle, Department of Environmental Immunology (I. Lehmann); IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf (U. Krämer); and Department of Pediatrics, Technical University, Munich (C.P. Bauer and U. Hoffman). This work was supported financially in part by the “Kompetenznetz Adipositas” (“Competence Network Obesity”), which is funded by the German Federal Ministry of Education and Research (FKZ: 01GI0826) and by the Munich Center of Health Sciences (MCHEALTH). The LACHY project was supported by NIH grant HL64157. The LEIPZIG study was supported by German Research Council (DFG) CRC 1052 “Obesity Mechanisms” C05, the Integrated Research and Treatment Centre (IFB) Adiposity Diseases, the European Commission Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO under grant agreement no. 279153, and the LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, subproject B1 LIFE Child, funded by the European Union, by the European Regional Development Fund (EFRE), and by the Free State of Saxony within the framework of the excellence initiative. The PANIC study was financially supported by grants from the Ministry of Social Affairs and Health of Finland, the Ministry of Education and Culture of Finland, the University of Eastern Finland, the Finnish Innovation Fund Sitra, the Social Insurance Institution of Finland, the Finnish Cultural Foundation, the Juho Vainio Foundation, the Foundation for Paediatric Research, the Paavo Nurmi Foundation, the Paulo Foundation, the Diabetes Research Foundation, the City of Kuopio, the Kuopio University Hospital (EVO-funding no. 5031343), and the Research Committee of the Kuopio University Hospital Catchment Area (the State Research Funding). The authors thank Professor Satoshi Sasaki at the University of Tokyo for dietary assessment and Naoko Okayama of Yamaguchi University for genotyping in the SHUNAN study. The SWS study was supported by the Medical Research Council, the British Heart Foundation, the Food Standards Agency, and Arthritis Research UK. The authors thank the members of the Southampton Women's Survey team, including Cyrus Cooper, Keith Godfrey, and Sian Robinson, and the team of dedicated research nurses and ancillary staff. The authors thank the participants in the Southampton Women's Survey, who gave us so much of their time. The STRIP study was financially supported by the Academy of Finland (grants 206374 and 251360), the Juho Vainio Foundation, the Finnish Foundation for Cardiovascular Research, the Finnish Cultural Foundation, the Ministry of Education and Culture of Finland, the Sigrid Juselius Foundation, the Yrjö Jahnsson Foundation, the C.G. Sundell Foundation, Special Governmental Grants for Health Sciences Research, Turku University Hospital, the Foundation for Pediatric Research, and the Turku University Foundation. The TEENAGE study has been cofinanced by the European Union (European Social Fund [ESF]) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF)-Research Funding Program: Heracleitus II. Investing in Knowledge Society Through the European Social Fund. This work was funded by the Wellcome Trust (grant 098051). The authors thank all study participants and their families, as well as all volunteers for their contribution to this study. T.O.K. was supported by grant no. DFF-1333-00124 from the Danish Council for Independent Research. V.B. is supported by the Unity Through Knowledge Fund CONNECTIVITY PROGRAM (“Gaining Experience” grant 2A) and the National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia (BRAIN GAIN-Postdoctoral fellowship).
PY - 2015/2
Y1 - 2015/2
N2 - The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10−4), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10−4): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10−10) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.
AB - The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10−4), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10−4): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10−10) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.
UR - http://europepmc.org/abstract/med/25720386
U2 - 10.2337/db14-1629
DO - 10.2337/db14-1629
M3 - Journal article
C2 - 25720386
SN - 0012-1797
VL - 64
SP - 2467
EP - 2476
JO - Diabetes
JF - Diabetes
IS - 7
ER -
