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

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 S.ingh Ahluwalia, Jolanda M.A. Boer, Peng Chen, Makoto DaimonJohan 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

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6961-6972
Number of pages12
JournalHuman molecular genetics
Issue number25
StatePublished - Dec 20 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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