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Hum Mol Genet. 2014 Dec 20;23(25):6961-72. doi: 10.1093/hmg/ddu411. Epub 2014 Aug 7.

FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.

Author information

1
Department of Epidemiology, Albert Einstein College of Medicine, Bronx, NY, USA Department of Nutrition and.
2
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences and.
3
Department of Nutrition and.
4
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
5
Nutrition and Genomics Laboratory, Jean Mayer USDA HNRCA at Tufts University, Boston, MA, USA.
6
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
7
Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
8
Division of Preventive Medicine.
9
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
10
Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
11
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
12
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences and Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Danish Pediatric Asthma Center, Gentofte Hospital, The Capital Region, Copenhagen, Denmark.
13
Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
14
Saw Swee Hock School of Public Health and.
15
Department of Endocrinology and Metabolism, Graduate School of Medicine, Hirosaki University, Hirosaki, Aomori, Japan Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Yamagata, Japan.
16
Department of General Practice and Primary Health Care National Institute for Health and Welfare, Helsinki, Finland.
17
Institute for Molecular Medicine National Institute for Health and Welfare, Helsinki, Finland Estonian Genome Center, University of Tartu, Tartu, Estonia.
18
School of Public Health, The Hebrew University of Jerusalem, Jerusalem, Israel.
19
Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
20
The Generation R Study Group Department of Epidemiology Department of Pediatrics.
21
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
22
Department of Internal Medicine, Section on Gerontology and Geriatric Medicine.
23
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, EC1M 6BQ London, UK.
24
Department of Preventive Medicine, Dong-A University College of Medicine, Busan, Korea.
25
National Institute for Health and Welfare, Helsinki, Finland.
26
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
27
USC Office of Population Studies Foundation, Inc., University of San Carlos, Cebu, Philippines.
28
Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
29
Cardiovascular Health Research Unit, Department of Medicine and.
30
Shanghai Institute of Preventive Medicine, Shanghai, China.
31
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.
32
Center for Public Health Genomics Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
33
Institute of Social and Preventive Medicine, Bâtiment Biopôle 2, Route de la Corniche 10, CH-1010 Lausanne, Switzerland Department of Medicine, CHUV, Rue du Bugnon 21, CH-1011 Lausanne, Switzerland.
34
Department of Epidemiology Center for Observational Research, Amgen, Inc., Thousand Oaks, CA, USA.
35
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
36
Department of Kinesiology, Laval University, Ste-Foy, QC, Canada.
37
Department of Epidemiology The Netherlands Genomics Initiative sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden, The Netherlands.
38
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
39
Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
40
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China.
41
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
42
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK National Institute for Health Research Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK National Institute for Health Research Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford OX3 7LE, UK.
43
Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece.
44
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, EC1M 6BQ London, UK Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD) and.
45
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
46
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences and.
47
The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
48
Department of Odontology and.
49
Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.
50
Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Yamagata, Japan.
51
Department of Preventive Medicine, HanYang University College of Medicine, Seoul, Korea.
52
Department of Epidemiology, Division of Public Health Sciences.
53
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston Salem, NC, USA.
54
Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
55
Department of Nutrition and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine Division of Cardiovascular Medicine Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
56
Department of Epidemiology Carolina Center for Genome Sciences.
57
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.
58
National Institute for Health and Welfare, Helsinki, Finland Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria Instituto de Investigacion Sanitaria del Hospital Universario LaPaz (IdiPAZ), Madrid, Spain.
59
Department of Epidemiology The Netherlands Genomics Initiative sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden, The Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
60
The Netherlands Genomics Initiative sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden, The Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
61
Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
62
Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA.
63
Department of Medicine, CHUV, Rue du Bugnon 21, CH-1011 Lausanne, Switzerland.
64
Division of Preventive Medicine Division of Cardiovascular Medicine.
65
Channing Division of Network Medicine, Department of Medicine.
66
Department of Nutrition and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
67
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine.
68
Channing Division of Network Medicine, Department of Medicine Department of Ophthalmology, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
69
Department of Nutrition and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine.
70
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
71
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland Research Unit, Kuopio University Hospital, Kuopio, Finland.
72
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA The Framingham Heart Study, Framingham, MA, USA.
73
Department of Epidemiology, Albert Einstein College of Medicine, Bronx, NY, USA.
74
Division of Preventive Medicine Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
75
Department of Nutrition and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden Department of Public Health and Clinical Medicine, Genetic Epidemiology and Clinical Research Group, Umeå University, Umeå, Sweden.
76
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences and Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
77
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK 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, Mount Sinai School of Medicine, New York City, NY, USA and.
78
Division of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas Health Science Center, Houston, TX, USA.
79
Department of Nutrition and Channing Division of Network Medicine, Department of Medicine nhlqi@channing.harvard.edu.

Abstract

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

PMID:
25104851
PMCID:
PMC4271061
DOI:
10.1093/hmg/ddu411
[Indexed for MEDLINE]
Free PMC Article

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