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

Publication

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

Journal Paper/Review - Aug 7, 2014

Hansen Torben, 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, Mikkilä Vera, Long Jirong, Lohman Kurt K, Christiansen Lene, Hofman Albert, Johansson Ingegerd, Jørgensen Torben, Karasawa Shigeru, Khaw Kay-Tee, Kim Mi-Kyung, Kristiansson Kati, Li Huaixing, Lin Xu, Liu Yongmei, Ou Shu Xiao, Siscovick David S, 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, Mohlke Karen L, Hunter David J, Pasquale Louis R, 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, Qi Lu, Forouhi Nita G, Qi Qibin, 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, Asif Ali Muhammad, Li Yanping, Liu Zhonghua, 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, Houston Denise K, Kanoni Stavroula, 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, Pérusse Louis, Ngwa Julius S, Monda Keri L, 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, Ferrucci Luigi

Citation

Hansen T, Mozaffarian D, North K, Pedersen O, Raitakari O, Rissanen H, Tuomilehto J, Van der Schouw Y, Uitterlinden A, Zillikens M, Franco O, Shyong Tai E, Mikkilä V, Long J, Lohman K, Christiansen L, Hofman A, Johansson I, Jørgensen T, Karasawa S, Khaw K, Kim M, Kristiansson K, Li H, Lin X, Liu Y, Ou Shu X, Siscovick D, Uusitupa M, Cupples L, Rankinen T, Orho-Melander M, Wang T, Chasman D, Franks P, Sørensen T, Hu F, Loos R, Nettleton J, Mohlke K, Hunter D, Pasquale L, Toft U, Verschuren W, Vollenweider P, Wareham N, Witteman J, Zheng W, Ridker P, Kang J, Liang L, Jensen M, Curhan G, Qi L, Forouhi N, Qi Q, Xu M, Ahluwalia T, Boer J, Chen P, Daimon M, Eriksson J, Perola M, Friedlander Y, Gao Y, Heppe D, Holloway J, Asif Ali M, Li Y, Liu Z, Kilpeläinen T, Downer M, Tanaka T, Smith C, Sluijs I, Sonestedt E, Chu A, Renström F, Lin X, Ängquist L, Huang J, Houston D, Kanoni S, van Rooij F, Xiang Y, Wen W, Wojczynski M, Zhu J, Borecki I, Bouchard C, Cai Q, Cooper C, Dedoussis G, Deloukas P, Pérusse L, Ngwa J, Monda K, Kim Y, Laaksonen M, Jääskeläinen T, Lee N, Lehtimäki T, Lemaitre R, Lu W, Luben R, Manichaikul A, Männistö S, Marques-Vidal P, Ferrucci L. FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals. Hum Mol Genet 2014; 23:6961-72.

Type

Journal Paper/Review (English)

Journal

Hum Mol Genet 2014; 23

Publication Date

Aug 7, 2014

Issn Electronic

1460-2083

Pages

6961-72

Brief description/objective

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.