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

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

doi:10.1093/hmg/ddu411

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

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

Epidemiology & Population Health

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138 Scopus citations

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.

Original language	English (US)
Pages (from-to)	6961-6972
Number of pages	12
Journal	Human molecular genetics
Volume	23
Issue number	25
DOIs	https://doi.org/10.1093/hmg/ddu411
State	Published - Dec 20 2014

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/hmg/ddu411

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Qi, Q., Kilpeläinen, T. O., Downer, M. K., Tanaka, T., Smith, C. E., Sluijs, I., Sonestedt, E., Chu, A. Y., Renström, F., Lin, X., Ängquist, L. H., Huang, J., Liu, Z., Li, Y., Asif Ali, M., Xu, M., Ahluwalia, T. S. I., Boer, J. M. A., Chen, P., ... Qi, L. (2014). FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals. Human molecular genetics, 23(25), 6961-6972. https://doi.org/10.1093/hmg/ddu411

Qi, Q, Kilpeläinen, TO, Downer, MK, Tanaka, T, Smith, CE, Sluijs, I, Sonestedt, E, Chu, AY, Renström, F, Lin, X, Ängquist, LH, Huang, J, Liu, Z, Li, Y, Asif Ali, M, Xu, M, Ahluwalia, TSI, Boer, JMA, Chen, P, Daimon, M, Eriksson, J, Perola, M, Friedlander, Y, Gao, YT, Heppe, DHM, Holloway, JW, Houston, DK, Kanoni, S, Kim, YM, 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, YB, 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, KT, Kim, MK, 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, MC, Franco, OH, Shyong Tai, E, Ou Shu, X, Siscovick, DS, Toft, U, Verschuren, WMM, 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, LA, Rankinen, T, Orho-Melander, M, Wang, T, Chasman, DI, Franks, PW, Sørensen, TIA, Hu, FB, Loos, RJF, Nettleton, JA & Qi, L 2014, 'FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals', Human molecular genetics, vol. 23, no. 25, pp. 6961-6972. https://doi.org/10.1093/hmg/ddu411

@article{c07acc76ea444d7b8e6ccc6adae90780,

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

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.",

author = "Qibin Qi and Kilpel{\"a}inen, {Tuomas O.} and Downer, {Mary K.} and Toshiko Tanaka and Smith, {Caren E.} and Ivonne Sluijs and Emily Sonestedt and Chu, {Audrey Y.} and Frida Renstr{\"o}m and Xiaochen Lin and {\"A}ngquist, {Lars H.} and Jinyan Huang and Zhonghua Liu and Yanping Li and {Asif Ali}, Muhammad and Min Xu and Ahluwalia, {Tarunveer S.ingh} and Boer, {Jolanda M.A.} and Peng Chen and Makoto Daimon and Johan Eriksson and Markus Perola and Yechiel Friedlander and Gao, {Yu Tang} and Heppe, {Denise H.M.} and Holloway, {John W.} and Houston, {Denise K.} and Stavroula Kanoni and Kim, {Yu Mi} and Laaksonen, {Maarit A.} and Tiina J{\"a}{\"a}skel{\"a}inen and Lee, {Nanette R.} and Terho Lehtim{\"a}ki and Lemaitre, {Rozenn N.} and Wei Lu and Luben, {Robert N.} and Ani Manichaikul and Satu M{\"a}nnist{\"o} and Pedro Marques-Vidal and Monda, {Keri L.} and Ngwa, {Julius S.} and Louis Perusse and {van Rooij}, {Frank J.A.} and Xiang, {Yong Bing} and Wanqing Wen and Wojczynski, {Mary K.} and Jingwen Zhu and Borecki, {Ingrid B.} and Claude Bouchard and Qiuyin Cai and Cyrus Cooper and Dedoussis, {George V.} and Panos Deloukas and Luigi Ferrucci and Forouhi, {Nita G.} and Torben Hansen and Lene Christiansen and Albert Hofman and Ingegerd Johansson and Torben J{\o}rgensen and Shigeru Karasawa and Khaw, {Kay Tee} and Kim, {Mi Kyung} and Kati Kristiansson and Huaixing Li and Xu Lin and Yongmei Liu and Lohman, {Kurt K.} and Jirong Long and Vera Mikkil{\"a} and Dariush Mozaffarian and Kari North and Oluf Pedersen and Olli Raitakari and Harri Rissanen and Jaakko Tuomilehto 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 Ulla Toft and Verschuren, {W. M.Monique} and Peter Vollenweider and Wareham, {Nicholas J.} and Witteman, {Jacqueline C.M.} and Wei Zheng and Ridker, {Paul M.} and Kang, {Jae H.} and Liming Liang and Jensen, {Majken K.} and Curhan, {Gary C.} and Pasquale, {Louis R.} and Hunter, {David J.} and Mohlke, {Karen L.} and Matti Uusitupa and Cupples, {L. Adrienne} and Tuomo Rankinen and Marju Orho-Melander and Tao Wang 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 Lu Qi",

year = "2014",

month = dec,

day = "20",

doi = "10.1093/hmg/ddu411",

language = "English (US)",

volume = "23",

pages = "6961--6972",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "25",

}

TY - JOUR

T1 - FTO genetic variants, dietary intake and body mass index

T2 - insights from 177,330 individuals

AU - Qi, Qibin

AU - Kilpeläinen, Tuomas O.

AU - Downer, Mary K.

AU - Tanaka, Toshiko

AU - Smith, Caren E.

AU - Sluijs, Ivonne

AU - Sonestedt, Emily

AU - Chu, Audrey Y.

AU - Renström, Frida

AU - Lin, Xiaochen

AU - Ängquist, Lars H.

AU - Huang, Jinyan

AU - Liu, Zhonghua

AU - Li, Yanping

AU - Asif Ali, Muhammad

AU - Xu, Min

AU - Ahluwalia, Tarunveer S.ingh

AU - Boer, Jolanda M.A.

AU - Chen, Peng

AU - Daimon, Makoto

AU - Eriksson, Johan

AU - Perola, Markus

AU - Friedlander, Yechiel

AU - Gao, Yu Tang

AU - Heppe, Denise H.M.

AU - Holloway, John W.

AU - Houston, Denise K.

AU - Kanoni, Stavroula

AU - Kim, Yu Mi

AU - Laaksonen, Maarit A.

AU - Jääskeläinen, Tiina

AU - Lee, Nanette R.

AU - Lehtimäki, Terho

AU - Lemaitre, Rozenn N.

AU - Lu, Wei

AU - Luben, Robert N.

AU - Manichaikul, Ani

AU - Männistö, Satu

AU - Marques-Vidal, Pedro

AU - Monda, Keri L.

AU - Ngwa, Julius S.

AU - Perusse, Louis

AU - van Rooij, Frank J.A.

AU - Xiang, Yong Bing

AU - Wen, Wanqing

AU - Wojczynski, Mary K.

AU - Zhu, Jingwen

AU - Borecki, Ingrid B.

AU - Bouchard, Claude

AU - Cai, Qiuyin

AU - Cooper, Cyrus

AU - Dedoussis, George V.

AU - Deloukas, Panos

AU - Ferrucci, Luigi

AU - Forouhi, Nita G.

AU - Hansen, Torben

AU - Christiansen, Lene

AU - Hofman, Albert

AU - Johansson, Ingegerd

AU - Jørgensen, Torben

AU - Karasawa, Shigeru

AU - Khaw, Kay Tee

AU - Kim, Mi Kyung

AU - Kristiansson, Kati

AU - Li, Huaixing

AU - Lin, Xu

AU - Liu, Yongmei

AU - Lohman, Kurt K.

AU - Long, Jirong

AU - Mikkilä, Vera

AU - Mozaffarian, Dariush

AU - North, Kari

AU - Pedersen, Oluf

AU - Raitakari, Olli

AU - Rissanen, Harri

AU - Tuomilehto, Jaakko

AU - van der Schouw, Yvonne T.

AU - Uitterlinden, André G.

AU - Zillikens, M. Carola

AU - Franco, Oscar H.

AU - Shyong Tai, E.

AU - Ou Shu, Xiao

AU - Siscovick, David S.

AU - Toft, Ulla

AU - Verschuren, W. M.Monique

AU - Vollenweider, Peter

AU - Wareham, Nicholas J.

AU - Witteman, Jacqueline C.M.

AU - Zheng, Wei

AU - Ridker, Paul M.

AU - Kang, Jae H.

AU - Liang, Liming

AU - Jensen, Majken K.

AU - Curhan, Gary C.

AU - Pasquale, Louis R.

AU - Hunter, David J.

AU - Mohlke, Karen L.

AU - Uusitupa, Matti

AU - Cupples, L. Adrienne

AU - Rankinen, Tuomo

AU - Orho-Melander, Marju

AU - Wang, Tao

AU - Chasman, Daniel I.

AU - Franks, Paul W.

AU - Sørensen, Thorkild I.A.

AU - Hu, Frank B.

AU - Loos, Ruth J.F.

AU - Nettleton, Jennifer A.

AU - Qi, Lu

PY - 2014/12/20

Y1 - 2014/12/20

N2 - 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.

AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84914107948&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddu411

DO - 10.1093/hmg/ddu411

M3 - Article

C2 - 25104851

AN - SCOPUS:84914107948

SN - 0964-6906

VL - 23

SP - 6961

EP - 6972

JO - Human molecular genetics

JF - Human molecular genetics

IS - 25

ER -

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

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