Title | FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Qi, Q, Kilpeläinen, TO, Downer, MK, Tanaka, T, Smith, CE, Sluijs, I, Sonestedt, E, Chu, AY, Renstrom, F, Lin, X, Ängquist, LH, Huang, J, Liu, Z, Li, Y, Ali, MAsif, Xu, M, Ahluwalia, TSingh, Boer, JMA, Chen, P, Daimon, M, Eriksson, J, Perola, M, Friedlander, Y, Gao, Y-T, Heppe, DHM, Holloway, JW, Houston, DK, Kanoni, S, Kim, Y-M, Laaksonen, MA, Jääskeläinen, T, Lee, NR, Lehtimäki, T, Lemaitre, RN, Lu, W, Luben, RN, Manichaikul, A, Männistö, S, Marques-Vidal, P, Monda, KL, Ngwa, JS, Perusse, L, van Rooij, FJA, Xiang, Y-B, Wen, W, Wojczynski, MK, Zhu, J, Borecki, IB, Bouchard, C, Cai, Q, Cooper, C, Dedoussis, GV, Deloukas, P, Ferrucci, L, Forouhi, NG, Hansen, T, Christiansen, L, Hofman, A, Johansson, I, Jørgensen, T, Karasawa, S, Khaw, K-T, Kim, M-K, Kristiansson, K, Li, H, Lin, X, Liu, Y, Lohman, KK, Long, J, Mikkilä, V, Mozaffarian, D, North, K, Pedersen, O, Raitakari, O, Rissanen, H, Tuomilehto, J, van der Schouw, YT, Uitterlinden, AG, Zillikens, CM, Franco, OH, E Tai, S, Shu, XOu, Siscovick, DS, Toft, U, Verschuren, WMMonique, Vollenweider, P, Wareham, NJ, Witteman, JCM, Zheng, W, Ridker, PM, Kang, JH, Liang, L, Jensen, MK, Curhan, GC, Pasquale, LR, Hunter, DJ, Mohlke, KL, Uusitupa, M, Cupples, AL, Rankinen, T, Orho-Melander, M, Wang, T, Chasman, DI, Franks, PW, Sørensen, TIA, Hu, FB, Loos, RJF, Nettleton, JA, Qi, L |
Journal | Hum Mol Genet |
Volume | 23 |
Issue | 25 |
Pagination | 6961-72 |
Date Published | 2014 Dec 20 |
ISSN | 1460-2083 |
Keywords | Adult, African Americans, Aged, Alleles, Asian Continental Ancestry Group, Body Mass Index, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Energy Intake, European Continental Ancestry Group, Female, Gene Frequency, Humans, Male, Middle Aged, Obesity, Polymorphism, Single Nucleotide, Proteins |
Abstract | <p>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.</p> |
DOI | 10.1093/hmg/ddu411 |
Alternate Journal | Hum. Mol. Genet. |
PubMed ID | 25104851 |
PubMed Central ID | PMC4271061 |
Grant List | 14136 / / Cancer Research UK / United Kingdom 17702 / / Arthritis Research UK / United Kingdom 263 MD 821336 / MD / NIMHD NIH HHS / United States 263 MD 9164 / MD / NIMHD NIH HHS / United States 5P30DK46200 / DK / NIDDK NIH HHS / United States 5R01 DK06833603 / DK / NIDDK NIH HHS / United States 5R01 DK07568102 / DK / NIDDK NIH HHS / United States 5R01 HL08770003 / HL / NHLBI NIH HHS / United States 5R01 HL08821502 / HL / NHLBI NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States CA047988 / CA / NCI NIH HHS / United States CA055075 / CA / NCI NIH HHS / United States CA49449 / CA / NCI NIH HHS / United States CA87969 / CA / NCI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States DK078150 / DK / NIDDK NIH HHS / United States DK080140 / DK / NIDDK NIH HHS / United States DK091718 / DK / NIDDK NIH HHS / United States DK46200 / DK / NIDDK NIH HHS / United States DK56350 / DK / NIDDK NIH HHS / United States DK58845 / DK / NIDDK NIH HHS / United 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