@article {6938, title = {FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.}, journal = {Hum Mol Genet}, volume = {23}, year = {2014}, month = {2014 Dec 20}, pages = {6961-72}, 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 {\texttimes} 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 {\texttimes} 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 {\texttimes} 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 {\texttimes} 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.

}, 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}, issn = {1460-2083}, doi = {10.1093/hmg/ddu411}, author = {Qi, Qibin and Kilpel{\"a}inen, Tuomas O and Downer, Mary K and Tanaka, Toshiko and Smith, Caren E and Sluijs, Ivonne and Sonestedt, Emily and Chu, Audrey Y and Renstrom, Frida and Lin, Xiaochen and {\"A}ngquist, Lars H and Huang, Jinyan and Liu, Zhonghua and Li, Yanping and Asif Ali, Muhammad and Xu, Min and Ahluwalia, Tarunveer Singh and Boer, Jolanda M A and Chen, Peng and Daimon, Makoto and Eriksson, Johan and Perola, Markus and Friedlander, Yechiel and Gao, Yu-Tang and Heppe, Denise H M and Holloway, John W and Houston, Denise K and Kanoni, Stavroula and Kim, Yu-Mi and Laaksonen, Maarit A and J{\"a}{\"a}skel{\"a}inen, Tiina and Lee, Nanette R and Lehtim{\"a}ki, Terho and Lemaitre, Rozenn N and Lu, Wei and Luben, Robert N and Manichaikul, Ani and M{\"a}nnist{\"o}, Satu and Marques-Vidal, Pedro and Monda, Keri L and Ngwa, Julius S and Perusse, Louis and van Rooij, Frank J A and Xiang, Yong-Bing and Wen, Wanqing and Wojczynski, Mary K and Zhu, Jingwen and Borecki, Ingrid B and Bouchard, Claude and Cai, Qiuyin and Cooper, Cyrus and Dedoussis, George V and Deloukas, Panos and Ferrucci, Luigi and Forouhi, Nita G and Hansen, Torben and Christiansen, Lene and Hofman, Albert and Johansson, Ingegerd and J{\o}rgensen, Torben and Karasawa, Shigeru and Khaw, Kay-Tee and Kim, Mi-Kyung and Kristiansson, Kati and Li, Huaixing and Lin, Xu and Liu, Yongmei and Lohman, Kurt K and Long, Jirong and Mikkil{\"a}, Vera and Mozaffarian, Dariush and North, Kari and Pedersen, Oluf and Raitakari, Olli and Rissanen, Harri and Tuomilehto, Jaakko and van der Schouw, Yvonne T and Uitterlinden, Andr{\'e} G and Zillikens, M Carola and Franco, Oscar H and Shyong Tai, E and Ou Shu, Xiao and Siscovick, David S and Toft, Ulla and Verschuren, W M Monique and Vollenweider, Peter and Wareham, Nicholas J and Witteman, Jacqueline C M and Zheng, Wei and Ridker, Paul M and Kang, Jae H and Liang, Liming and Jensen, Majken K and Curhan, Gary C and Pasquale, Louis R and Hunter, David J and Mohlke, Karen L and Uusitupa, Matti and Cupples, L Adrienne and Rankinen, Tuomo and Orho-Melander, Marju and Wang, Tao and Chasman, Daniel I and Franks, Paul W and S{\o}rensen, Thorkild I A and Hu, Frank B and Loos, Ruth J F and Nettleton, Jennifer A and Qi, Lu} }