title: Dietary Intake, FTO Genetic Variants, and Adiposity: A Combined Analysis of Over 16,000 Children and Adolescents.
abstract: 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.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY Department of Nutrition, Harvard School of Public Health, Boston, MA qibin.qi@einstein.yu.edu nhlqi@channing.harvard.edu.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Downer
authors.affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital and University of Cambridge, Cambridge, U.K. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tuomas O
authors.initials: TO
authors.lastname: Kilpeläinen
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Department of Pediatrics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: H Rob
authors.initials: HR
authors.lastname: Taal
authors.affiliation: MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton, U.K.
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Barton
authors.affiliation: Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece Department of Health Sciences, University of Leicester, Leicester, U.K.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Ntalla
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Standl
authors.affiliation: Wellcome Trust Sanger Institute, Hixton, Cambridge, U.K. Department of Medical Biology, University of Split School of Medicine, Split, Croatia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Boraska
authors.affiliation: Institute of Health Sciences, University of Oulu, Oulu, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Huikari
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Global Public Health, Leiden University College, Hague, the Netherlands.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kiefte-de Jong
authors.affiliation: Pediatric Research Center, Department of Women's & Child Health, University of Leipzig, Leipzig, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Körner
authors.affiliation: Institute of Biomedicine, Department of Physiology, University of Eastern Finland, Kuopio, Finland Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
authors.forename: Timo A
authors.initials: TA
authors.lastname: Lakka
authors.affiliation: Department of Neurology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Gaifen
authors.initials: G
authors.lastname: Liu
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, and Sachs' Children and Youth Hospital, Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Magnusson
authors.affiliation: Graduate School of Science and Engineering, Yamaguchi University, Ube, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Okuda
authors.affiliation: The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, U.K.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Richmond
authors.affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital and University of Cambridge, Cambridge, U.K.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Scott
authors.affiliation: School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, U.K.
authors.forename: Mark E S
authors.initials: ME
authors.lastname: Bailey
authors.affiliation: Pediatric Research Center, Department of Women's & Child Health, University of Leipzig, Leipzig, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Scheuermann
authors.affiliation: Human Genetics and Medical Genomics, Faculty of Medicine, University of Southampton, Southampton, U.K.
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.affiliation: MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton, U.K.
authors.forename: Hazel
authors.initials: H
authors.lastname: Inskip
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Isasi
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Mossavar-Rahmani
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Department of Pediatrics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Finnish Institute of Occupational Health, Oulu, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Laitinen
authors.affiliation: Institute of Biomedicine, Department of Physiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Virpi
authors.initials: V
authors.lastname: Lindi
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, and Sachs' Children and Youth Hospital, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.affiliation: School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, U.K.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Pitsiladis
authors.affiliation: The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Pitkänen
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands Georgia Prevention Center, Department of Pediatrics, Georgia Regents University, Augusta, GA.
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, U.K.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Hokkaido Nursing College, Chuo-ku, Sapporo, Japan.
authors.forename: Hinoda
authors.initials: H
authors.lastname: Yuji
authors.affiliation: Wellcome Trust Sanger Institute, Hixton, Cambridge, U.K.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.affiliation: Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
authors.forename: George V
authors.initials: GV
authors.lastname: Dedoussis
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Judith
authors.initials: J
authors.lastname: Wylie-Rosett
authors.affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital and University of Cambridge, Cambridge, U.K. The Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY.
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA Department of Epidemiology, Harvard School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA qibin.qi@einstein.yu.edu nhlqi@channing.harvard.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D050154:Adiposity; D000293:Adolescent; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004044:Dietary Proteins / Q000008:administration & dosage; D002149:Energy Intake; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: D004044:Dietary Proteins; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human