Qibin Qi, Tuomas O. Kilpeläinen, Mary K. Downer, Toshiko Tanaka, Caren E. Smith, Ivonne Sluijs, Emily Sonestedt, Audrey Y. Chu, Frida Renström, Xiaochen Lin, Lars H. Ängquist, Jinyan Huang, Zhonghua Liu, Yanping Li, Muhammad Asif Ali, Min Xu, Tarunveer Singh Ahluwalia, Jolanda M.A. Boer, Peng Chen, Makoto Daimon, Johan Eriksson, Markus Perola, Yechiel Friedlander, Yu-Tang Gao, Denise H.M. Heppe, John W. Holloway, Denise K. Houston, Stavroula Kanoni, Yu-Mi Kim, Maarit A. Laaksonen, Tiina Jääskeläinen, Nanette R. Lee, Terho Lehtimäki, Rozenn N. Lemaitre, Wei Lu, Robert N. Luben, Ani Manichaikul, Satu Männistö, Pedro Marques-Vidal, Keri L. Monda, Julius S. Ngwa, Louis Perusse, Frank J.A. Van Rooij, Yong-Bing Xiang, Wanqing Wen, Mary K Wojczynski, Jingwen Zhu, Ingrid B. Borecki, Claude Bouchard, Qiuyin Cai, Cyrus Cooper, George V. Dedoussis, Panos Deloukas, Luigi Ferrucci, Nita G. Forouhi, Torben Hansen, Lene Christiansen, Albert Hofman, Ingegerd Johansson, Torben Jørgensen, Shigeru Karasawa, Kay-Tee Khaw, Mi-Kyung Kim, Kati Kristiansson, Huaixing Li, Xu Lin, Yongmei Liu, Kurt K. Lohman, Jirong Long, Vera Mikkilä, Dariush Mozaffarian, Kari North, Oluf Pedersen, Olli Raitakari, Harri Rissanen, Jaakko Tuomilehto, Yvonne T. Van Der Schouw, André G. Uitterlinden, M. Carola Zillikens, Oscar H. Franco, E. Shyong Tai, Xiao Ou Shu, David S. Siscovick, Ulla Toft, W.M. Monique Verschuren, Peter Vollenweider, Nicholas J. Wareham, Jacqueline C.M. Witteman, Wei Zheng, Paul M. Ridker, Jae H. Kang, Liming Liang, Majken K. Jensen, Gary C. Curhan, Louis R. Pasquale, David J. Hunter, Karen L. Mohlke, Matti Uusitupa, L. Adrienne Cupples, Tuomo Rankinen, Marju Orho-Melander, Tao Wang, Daniel I. Chasman, Paul W. Franks, Thorkild I.A. Sørensen, Frank B. Hu, Ruth J. F. Loos, Jennifer A. Nettleton, Lu Qi
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/m2, P = 1.9 × 10-105), and all participants (0.30 [0.30, 0.35] kg/m2, 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. © 2014 The Author. Published by Oxford University Press. All rights reserved.
Department of Epidemiology, Albert Einstein College of Medicine, Bronx, NY, United States; Department of Nutrition, Harvard School of Public Health, Boston, MA, United States; Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States; MRC Epidemiology Unit, University of Cambridge, School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, United States; Nutrition and Genomics Laboratory, Jean Mayer USDA HNRCA, Tufts University, Boston, MA, United States; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden; Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark; State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated, Shanghai Jiao Tong University, School of Medicine, Shanghai, China; Danish Pediatric Asthma Center, Gentofte Hospital, The Capital Region, Copenhagen, Denmark; Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, Netherlands; Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore; Department of Endocrinology and Metabolism, Graduate School of Medicine, Hirosaki University, Aomori, Hirosaki, Japan; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University, Faculty of Medicine, Yamagata, Japan; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland; Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland; Estonian Genome Center, University of Tartu, Tartu, Estonia; School of Public Health, The Hebrew University of Jerusalem, Jerusalem, Israel; Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China; The Generation R Study Group, Erasmus Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Pediatrics, Erasmus Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston Salem, NC, United States; Department of Epidemiology, Division of Public Health Sciences, Wake Forest School of Medicine, Winston Salem, NC, United States; Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston Salem, NC, United States; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, United Kingdom; Department of Preventive Medicine, Dong-A University College of Medicine, Busan, South Korea; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; USC Office of Population Studies Foundation, Inc., University of San Carlos, Cebu, Philippines; Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States; Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, United States; Shanghai Institute of Preventive Medicine, Shanghai, China; Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States; Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, United States; Institute of Social and Preventive Medicine, Bâtiment Biopôle 2, Route de la Corniche 10, Lausanne, CH-1010, Switzerland; Department of Medicine, CHUV, Rue du Bugnon 21, Lausanne, CH-1011, Switzerland; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, United States; Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, United States; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Center for Observational Research, Amgen, Inc., Thousand Oaks, CA, United States; Department of Biostatistics, Boston University, School of Public Health, Boston, MA, United States; Department of Kinesiology, Laval University, Ste-Foy, QC, Canada; The Netherlands Genomics Initiative Sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden, Netherlands; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, School of Medicine, Nashville, TN, United States; Department of Genetics, Washington University, School of Medicine, St. Louis, MO, United States; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China; Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, United Kingdom; National Institute for Health Research, Biomedical Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, United Kingdom; National Institute for Health Research, Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, OX3 7LE, United Kingdom; Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece; Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, 21589, Saudi Arabia; Diabetes Research Group, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark; Department of Odontology, Genetic Epidemiology and Clinical Research Group, Umeå University, Umeå, Sweden; Department of Public Health and Clinical Medicine, Genetic Epidemiology and Clinical Research Group, Umeå University, Umeå, Sweden; Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark; Department of Preventive Medicine, HanYang University, College of Medicine, Seoul, South Korea; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, United States; Department of Clinical Physiology and Nuclear Medicine, University of Turku, Turku University Hospital, Turku, Finland; Centre for Vascular Prevention, Danube-University Krems, Krems, 3500, Austria; Instituto de Investigacion Sanitaria Del Hospital Universario LaPaz (IdiPAZ), Madrid, Spain; Duke-National University of Singapore, Graduate Medical School, Singapore, Singapore; Department of Ophthalmology, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States; Research Unit, Kuopio University Hospital, Kuopio, Finland; The Framingham Heart Study, Framingham, MA, United States; 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, United States; Division of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas Health Science Center, Houston, TX, United States
