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FTO Genetic Variants, Dietary Intake and Body Mass Index: Insights from 177,330 Individuals – Cebu Longitudinal Health and Nutrition Survey

FTO Genetic Variants, Dietary Intake and Body Mass Index: Insights from 177,330 Individuals

Citation

Qi, Qibin; Kilpeläinen, Tuomas O.; Downer, Mary K.; Tanaka, Toshiko; Smith, Caren E.; Sluijs, Ivonne; Sonestedt, Emily; Chu, Audrey Y.; Renström, Frida; & Lin, Xiaochen, et al. (2014). FTO Genetic Variants, Dietary Intake and Body Mass Index: Insights from 177,330 Individuals. Human Molecular Genetics, 23(25), 6961-6972.

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/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.

URL

http://dx.doi.org/10.1093/hmg/ddu411

Reference Type

Journal Article

Year Published

2014

Journal Title

Human Molecular Genetics

Author(s)

Qi, Qibin
Kilpeläinen, Tuomas O.
Downer, Mary K.
Tanaka, Toshiko
Smith, Caren E.
Sluijs, Ivonne
Sonestedt, Emily
Chu, Audrey Y.
Renström, Frida
Lin, Xiaochen
Ängquist, Lars H.
Huang, Jinyan
Liu, Zhonghua
Li, Yanping
Asif Ali, Muhammad
Xu, Min
Ahluwalia, Tarunveer Singh
Boer, Jolanda M.A.
Chen, Peng
Daimon, Makoto
Eriksson, Johan
Perola, Markus
Friedlander, Yechiel
Gao, Yu-Tang
Heppe, Denise H.M.
Holloway, John W.
Houston, Denise K.
Kanoni, Stavroula
Kim, Yu-Mi
Laaksonen, Maarit A.
Jääskeläinen, Tiina
Lee, Nanette R.
Lehtimäki, Terho
Lemaitre, Rozenn N.
Lu, Wei
Luben, Robert N.
Manichaikul, Ani
Männistö, Satu
Marques-Vidal, Pedro
Monda, Keri L.
Ngwa, Julius S.
Perusse, Louis
van Rooij, Frank J.A.
Xiang, Yong-Bing
Wen, Wanqing
Wojczynski, Mary K
Zhu, Jingwen
Borecki, Ingrid B.
Bouchard, Claude
Cai, Qiuyin
Cooper, Cyrus
Dedoussis, George V.
Deloukas, Panos
Ferrucci, Luigi
Forouhi, Nita G.
Hansen, Torben
Christiansen, Lene
Hofman, Albert
Johansson, Ingegerd
Jørgensen, Torben
Karasawa, Shigeru
Khaw, Kay-Tee
Kim, Mi-Kyung
Kristiansson, Kati
Li, Huaixing
Lin, Xu
Liu, Yongmei
Lohman, Kurt K.
Long, Jirong
Mikkilä, Vera
Mozaffarian, Dariush
North, Kari
Pedersen, Oluf
Raitakari, Olli
Rissanen, Harri
Tuomilehto, Jaakko
van der Schouw, Yvonne T.
Uitterlinden, André G.
Zillikens, M. Carola
Franco, Oscar H.
Shyong Tai, E.
Ou Shu, Xiao
Siscovick, David S.
Toft, Ulla
Verschuren, W.M. Monique
Vollenweider, Peter
Wareham, Nicholas J.
Witteman, Jacqueline C.M.
Zheng, Wei
Ridker, Paul M.
Kang, Jae H.
Liang, Liming
Jensen, Majken K.
Curhan, Gary C.
Pasquale, Louis R.
Hunter, David J.
Mohlke, Karen L.
Uusitupa, Matti
Cupples, L. Adrienne
Rankinen, Tuomo
Orho-Melander, Marju
Wang, Tao
Chasman, Daniel I.
Franks, Paul W.
Sørensen, Thorkild I.A.
Hu, Frank B.
Loos, Ruth J.F.
Nettleton, Jennifer A.
Qi, Lu