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

FTO genetic variants, dietary intake, and body mass index: insights from 177,330 individuals
FTO genetic variants, dietary intake, and body mass index: insights from 177,330 individuals
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.
6961-6972
Qi, Q.
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Kilpelainen, T. O.
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Downer, M. K.
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Tanaka, T.
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Smith, C. E.
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Sluijs, I.
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Sonestedt, E.
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Chu, A. Y.
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Renstrom, F.
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Lin, X.
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Angquist, L. H.
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Huang, J.
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Liu, Z.
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Li, Y.
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Asif Ali, M.
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Xu, M.
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Ahluwalia, T. S.
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Boer, J. M. A.
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Chen, P.
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Daimon, M.
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Eriksson, J.
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Perola, M.
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Friedlander, Y.
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Gao, Y.-T.
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Heppe, D. H. M.
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Holloway, J. W.
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Houston, D. K.
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Laaksonen, M. A.
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Lehtimaki, T.
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Lu, W.
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Luben, R. N.
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Manichaikul, A.
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Mannisto, S.
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Marques-Vidal, P.
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Monda, K. L.
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Ngwa, J. S.
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Perusse, L.
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van Rooij, F. J. A.
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Xiang, Y.-B.
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Wen, W.
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Wojczynski, M. K.
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Zhu, J.
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Borecki, I. B.
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Bouchard, C.
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Cai, Q.
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Cooper, C.
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Dedoussis, G. V.
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Deloukas, P.
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Ferrucci, L.
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Forouhi, N. G.
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Hansen, T.
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Christiansen, L.
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Hofman, A.
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Johansson, I.
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Jorgensen, T.
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Karasawa, S.
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Khaw, K.-T.
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Kristiansson, K.
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Li, H.
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Liu, Y.
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Lohman, K. K.
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Long, J.
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Mikkila, V.
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Mozaffarian, D.
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North, K.
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Pedersen, O.
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Raitakari, O.
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Rissanen, H.
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Tuomilehto, J.
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van der Schouw, Y. T.
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Uitterlinden, A. G.
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Zillikens, M. C.
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Franco, O. H.
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Tai, E. S.
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Shu, X. O.
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Siscovick, D. S.
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Toft, U.
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Verschuren, W. M. M.
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Vollenweider, P.
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Wareham, N. J.
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Witteman, J. C. M.
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Zheng, W.
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Ridker, P. M.
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Kang, J. H.
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Liang, L.
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Jensen, M. K.
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Curhan, G. C.
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Pasquale, L. R.
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Hunter, D. J.
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Mohlke, K. L.
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Uusitupa, M.
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Cupples, L. A.
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Rankinen, T.
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Orho-Melander, M.
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Chasman, D. I.
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Franks, P. W.
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Sorensen, T. I. A.
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Hu, F. B.
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Loos, R. J. F.
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Nettleton, J.
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Qi, L.
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Qi, Q.
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Kilpelainen, T. O.
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Downer, M. K.
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Tanaka, T.
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Smith, C. E.
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Sluijs, I.
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Sonestedt, E.
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Chu, A. Y.
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Renstrom, F.
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Lin, X.
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Angquist, L. H.
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Huang, J.
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Liu, Z.
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Li, Y.
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Asif Ali, M.
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Xu, M.
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Ahluwalia, T. S.
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Boer, J. M. A.
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Chen, P.
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Daimon, M.
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Eriksson, J.
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Perola, M.
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Friedlander, Y.
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Gao, Y.-T.
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Heppe, D. H. M.
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Holloway, J. W.
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Houston, D. K.
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Kanoni, S.
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Kim, Y.-M.
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Laaksonen, M. A.
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Jaaskelainen, T.
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Lee, N. R.
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Lehtimaki, T.
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Lemaitre, R. N.
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Lu, W.
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Luben, R. N.
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Manichaikul, A.
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Mannisto, S.
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Marques-Vidal, P.
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Monda, K. L.
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Ngwa, J. S.
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Perusse, L.
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van Rooij, F. J. A.
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Xiang, Y.-B.
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Wen, W.
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Zhu, J.
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Borecki, I. B.
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Bouchard, C.
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Cai, Q.
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Cooper, C.
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Dedoussis, G. V.
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Deloukas, P.
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Ferrucci, L.
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Forouhi, N. G.
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Hansen, T.
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Christiansen, L.
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Hofman, A.
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Johansson, I.
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Jorgensen, T.
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Karasawa, S.
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Khaw, K.-T.
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Kim, M.-K.
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Kristiansson, K.
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Li, H.
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Liu, Y.
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Lohman, K. K.
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Long, J.
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Mikkila, V.
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Mozaffarian, D.
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North, K.
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Pedersen, O.
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Raitakari, O.
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Rissanen, H.
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Tuomilehto, J.
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van der Schouw, Y. T.
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Uitterlinden, A. G.
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Zillikens, M. C.
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Franco, O. H.
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Tai, E. S.
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Shu, X. O.
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Siscovick, D. S.
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Toft, U.
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Verschuren, W. M. M.
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Vollenweider, P.
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Wareham, N. J.
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Witteman, J. C. M.
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Zheng, W.
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Ridker, P. M.
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Kang, J. H.
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Liang, L.
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Jensen, M. K.
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Curhan, G. C.
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Pasquale, L. R.
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Hunter, D. J.
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Mohlke, K. L.
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Uusitupa, M.
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Cupples, L. A.
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Rankinen, T.
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Orho-Melander, M.
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Chasman, D. I.
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Franks, P. W.
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Sorensen, T. I. A.
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Hu, F. B.
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Loos, R. J. F.
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Nettleton, J.
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Qi, L.
d1312bc6-c7fc-45e0-b75d-baaf78babbc1

Qi, Q., Kilpelainen, T. O., Downer, M. K., Tanaka, T., Smith, C. E., Sluijs, I., Sonestedt, E., Chu, A. Y., Renstrom, F., Lin, X., Angquist, L. H., Huang, J., Liu, Z., Li, Y., Asif Ali, M., Xu, M., Ahluwalia, T. S., Boer, J. M. A., Chen, P., Daimon, M., Eriksson, J., Perola, M., Friedlander, Y., Gao, Y.-T., Heppe, D. H. M., Holloway, J. W., Houston, D. K., Kanoni, S., Kim, Y.-M., Laaksonen, M. A., Jaaskelainen, T., Lee, N. R., Lehtimaki, T., Lemaitre, R. N., Lu, W., Luben, R. N., Manichaikul, A., Mannisto, S., Marques-Vidal, P., Monda, K. L., Ngwa, J. S., Perusse, L., van Rooij, F. J. A., Xiang, Y.-B., Wen, W., Wojczynski, M. K., Zhu, J., Borecki, I. B., Bouchard, C., Cai, Q., Cooper, C., Dedoussis, G. V., Deloukas, P., Ferrucci, L., Forouhi, N. G., Hansen, T., Christiansen, L., Hofman, A., Johansson, I., Jorgensen, T., Karasawa, S., Khaw, K.-T., Kim, M.-K., Kristiansson, K., Li, H., Liu, Y., Lohman, K. K., Long, J., Mikkila, V., Mozaffarian, D., North, K., Pedersen, O., Raitakari, O., Rissanen, H., Tuomilehto, J., van der Schouw, Y. T., Uitterlinden, A. G., Zillikens, M. C., Franco, O. H., Tai, E. S., Shu, X. O., Siscovick, D. S., Toft, U., Verschuren, W. M. M., Vollenweider, P., Wareham, N. J., Witteman, J. C. M., Zheng, W., Ridker, P. M., Kang, J. H., Liang, L., Jensen, M. K., Curhan, G. C., Pasquale, L. R., Hunter, D. J., Mohlke, K. L., Uusitupa, M., Cupples, L. A., Rankinen, T., Orho-Melander, M., Chasman, D. I., Franks, P. W., Sorensen, T. I. A., Hu, F. B., Loos, R. J. F., Nettleton, J. and Qi, L. (2014) FTO genetic variants, dietary intake, and body mass index: insights from 177,330 individuals. Human Molecular Genetics, 23 (25), 6961-6972. (doi:10.1093/hmg/ddu411). (PMID:25104851)

Record type: Article

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.

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Accepted/In Press date: 7 August 2014
Published date: 20 December 2014
Related URLs:
Organisations: Human Development & Health

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Local EPrints ID: 368011
URI: http://eprints.soton.ac.uk/id/eprint/368011
DOI: doi:10.1093/hmg/ddu411
PURE UUID: 6884d107-af5e-4efd-913a-d34ac95ba1b7
ORCID for J. W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 28 Aug 2014 10:05
Last modified: 15 Mar 2024 02:56

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Contributors

Author: Q. Qi
Author: T. O. Kilpelainen
Author: M. K. Downer
Author: T. Tanaka
Author: C. E. Smith
Author: I. Sluijs
Author: E. Sonestedt
Author: A. Y. Chu
Author: F. Renstrom
Author: X. Lin
Author: L. H. Angquist
Author: J. Huang
Author: Z. Liu
Author: Y. Li
Author: M. Asif Ali
Author: M. Xu
Author: T. S. Ahluwalia
Author: J. M. A. Boer
Author: P. Chen
Author: M. Daimon
Author: J. Eriksson
Author: M. Perola
Author: Y. Friedlander
Author: Y.-T. Gao
Author: D. H. M. Heppe
Author: J. W. Holloway ORCID iD
Author: D. K. Houston
Author: S. Kanoni
Author: Y.-M. Kim
Author: M. A. Laaksonen
Author: T. Jaaskelainen
Author: N. R. Lee
Author: T. Lehtimaki
Author: R. N. Lemaitre
Author: W. Lu
Author: R. N. Luben
Author: A. Manichaikul
Author: S. Mannisto
Author: P. Marques-Vidal
Author: K. L. Monda
Author: J. S. Ngwa
Author: L. Perusse
Author: F. J. A. van Rooij
Author: Y.-B. Xiang
Author: W. Wen
Author: M. K. Wojczynski
Author: J. Zhu
Author: I. B. Borecki
Author: C. Bouchard
Author: Q. Cai
Author: C. Cooper
Author: G. V. Dedoussis
Author: P. Deloukas
Author: L. Ferrucci
Author: N. G. Forouhi
Author: T. Hansen
Author: L. Christiansen
Author: A. Hofman
Author: I. Johansson
Author: T. Jorgensen
Author: S. Karasawa
Author: K.-T. Khaw
Author: M.-K. Kim
Author: K. Kristiansson
Author: H. Li
Author: Y. Liu
Author: K. K. Lohman
Author: J. Long
Author: V. Mikkila
Author: D. Mozaffarian
Author: K. North
Author: O. Pedersen
Author: O. Raitakari
Author: H. Rissanen
Author: J. Tuomilehto
Author: Y. T. van der Schouw
Author: A. G. Uitterlinden
Author: M. C. Zillikens
Author: O. H. Franco
Author: E. S. Tai
Author: X. O. Shu
Author: D. S. Siscovick
Author: U. Toft
Author: W. M. M. Verschuren
Author: P. Vollenweider
Author: N. J. Wareham
Author: J. C. M. Witteman
Author: W. Zheng
Author: P. M. Ridker
Author: J. H. Kang
Author: L. Liang
Author: M. K. Jensen
Author: G. C. Curhan
Author: L. R. Pasquale
Author: D. J. Hunter
Author: K. L. Mohlke
Author: M. Uusitupa
Author: L. A. Cupples
Author: T. Rankinen
Author: M. Orho-Melander
Author: D. I. Chasman
Author: P. W. Franks
Author: T. I. A. Sorensen
Author: F. B. Hu
Author: R. J. F. Loos
Author: J. Nettleton
Author: L. Qi

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