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

QB Qi; TO Kilpelainen; MK Downer; T Tanaka; CE Smith; Iris Sluijs; E Sonestedtl; AY Chull; F Renstrom; XC Lin; LH Angquist; JY Huang; ZH Liu; YP Li; MA Ali; M Xu; TS Ahluwalia; JMA Boer; P Chen; M Daimon; J Eriksson; M Perola; Y Friedlander; YT Gao; Denise Heppe; JW Holloway; DK Houston; S Kanoni; YM Kim; MA Laaksonen; T Jaaskelainen; NR Lee; T Lehtimaki; RN Lemaitre; W Lu; RN Luben; A Manichaiku; S Mannisto; P Marques-Vidal; KL Monda; JS Ngwa; L Perusse; FJA van Rooij; YB Xiang; WQ Wen; MK Wojczynski; JW Zhu; IB Borecki; C Bouchard; QY Cai; C Cooper; GV Dedoussis; P Deloukas; L Ferrucci; NG Forouhi; T Hansen; L Christiansen; Bert Hofman; I Johansson; T Jorgensen; S Karasawa; KT Khaw; MK Kim; K Kristiansson; HX Li; X Lin; YM Liu; KK Lohman; JR Long; V Mikkila; D Mozaffarian; K North; O Pedersen; O Raitakari; H Rissanen; J Tuomilehto; YT van der Schouw; André Uitterlinden; M.C. Zillikens; OH Franco Duran; ES Tai; XO Shu; DS Siscovick; U Toft; WMM Verschuren; P Vollenweider; NJ Wareham; JCM Witteman; W Zheng; PM Ridker; JH Kang; LM Liang; MK Jensen; GC Curhan; LR Pasquale; DJ Hunter; KL Mohlke; M Uusitupa; LA Cupples; T Rankinen; M Orho-Melander; Tianshi Wang; DI Chasman; PW Franks; TIA Sorensen; FB Hu; RJF Loos; JA Nettleton; L Qi

doi:10.1093/hmg/ddu411

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

QB Qi, TO Kilpelainen, MK Downer, T Tanaka, CE Smith, Iris Sluijs, E Sonestedtl, AY Chull, F Renstrom, XC Lin, LH Angquist, JY Huang, ZH Liu, YP Li, MA Ali, M Xu, TS Ahluwalia, JMA Boer, P Chen, M DaimonJ Eriksson, M Perola, Y Friedlander, YT Gao, Denise Heppe, JW Holloway, DK Houston, S Kanoni, YM Kim, MA Laaksonen, T Jaaskelainen, NR Lee, T Lehtimaki, RN Lemaitre, W Lu, RN Luben, A Manichaiku, S Mannisto, P Marques-Vidal, KL Monda, JS Ngwa, L Perusse, FJA van Rooij, YB Xiang, WQ Wen, MK Wojczynski, JW Zhu, IB Borecki, C Bouchard, QY Cai, C Cooper, GV Dedoussis, P Deloukas, L Ferrucci, NG Forouhi, T Hansen, L Christiansen, Bert Hofman, I Johansson, T Jorgensen, S Karasawa, KT Khaw, MK Kim, K Kristiansson, HX Li, X Lin, YM Liu, KK Lohman, JR Long, V Mikkila, D Mozaffarian, K North, O Pedersen, O Raitakari, H Rissanen, J Tuomilehto, YT van der Schouw, André Uitterlinden, M.C. Zillikens, OH Franco Duran, ES Tai, XO Shu, DS Siscovick, U Toft, WMM Verschuren, P Vollenweider, NJ Wareham, JCM Witteman, W Zheng, PM Ridker, JH Kang, LM Liang, MK Jensen, GC Curhan, LR Pasquale, DJ Hunter, KL Mohlke, M Uusitupa, LA Cupples, T Rankinen, M Orho-Melander, Tianshi Wang, DI Chasman, PW Franks, TIA Sorensen, FB Hu, RJF Loos, JA Nettleton, L Qi

Research output: Contribution to journal › Article › Academic › peer-review

131 Citations (Scopus)

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 BM I. 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 x 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 x 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 x 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 x 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	Undefined/Unknown
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
Publication status	Published - 2014

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10.1093/hmg/ddu411

Cite this

Qi, QB., Kilpelainen, TO., Downer, MK., Tanaka, T., Smith, CE., Sluijs, I., Sonestedtl, E., Chull, AY., Renstrom, F., Lin, XC., Angquist, LH., Huang, JY., Liu, ZH., Li, YP., Ali, MA., Xu, M., Ahluwalia, TS., Boer, JMA., 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

@article{6761034e73e8489499e219df7145111b,

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 BM I. 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 x 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 x 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 x 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 x 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 = "QB Qi and TO Kilpelainen and MK Downer and T Tanaka and CE Smith and Iris Sluijs and E Sonestedtl and AY Chull and F Renstrom and XC Lin and LH Angquist and JY Huang and ZH Liu and YP Li and MA Ali and M Xu and TS Ahluwalia and JMA Boer and P Chen and M Daimon and J Eriksson and M Perola and Y Friedlander and YT Gao and Denise Heppe and JW Holloway and DK Houston and S Kanoni and YM Kim and MA Laaksonen and T Jaaskelainen and NR Lee and T Lehtimaki and RN Lemaitre and W Lu and RN Luben and A Manichaiku and S Mannisto and P Marques-Vidal and KL Monda and JS Ngwa and L Perusse and {van Rooij}, FJA and YB Xiang and WQ Wen and MK Wojczynski and JW Zhu and IB Borecki and C Bouchard and QY Cai and C Cooper and GV Dedoussis and P Deloukas and L Ferrucci and NG Forouhi and T Hansen and L Christiansen and Bert Hofman and I Johansson and T Jorgensen and S Karasawa and KT Khaw and MK Kim and K Kristiansson and HX Li and X Lin and YM Liu and KK Lohman and JR Long and V Mikkila and D Mozaffarian and K North and O Pedersen and O Raitakari and H Rissanen and J Tuomilehto and {van der Schouw}, YT and Andr{\'e} Uitterlinden and M.C. Zillikens and {Franco Duran}, OH and ES Tai and XO Shu and DS Siscovick and U Toft and WMM Verschuren and P Vollenweider and NJ Wareham and JCM Witteman and W Zheng and PM Ridker and JH Kang and LM Liang and MK Jensen and GC Curhan and LR Pasquale and DJ Hunter and KL Mohlke and M Uusitupa and LA Cupples and T Rankinen and M Orho-Melander and Tianshi Wang and DI Chasman and PW Franks and TIA Sorensen and FB Hu and RJF Loos and JA Nettleton and L Qi",

year = "2014",

doi = "10.1093/hmg/ddu411",

language = "Undefined/Unknown",

volume = "23",

pages = "6961--6972",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "25",

}

Qi, QB, Kilpelainen, TO, Downer, MK, Tanaka, T, Smith, CE, Sluijs, I, Sonestedtl, E, Chull, AY, Renstrom, F, Lin, XC, Angquist, LH, Huang, JY, Liu, ZH, Li, YP, Ali, MA, Xu, M, Ahluwalia, TS, Boer, JMA, Chen, P, Daimon, M, Eriksson, J, Perola, M, Friedlander, Y, Gao, YT, Heppe, D, Holloway, JW, Houston, DK, Kanoni, S, Kim, YM, Laaksonen, MA, Jaaskelainen, T, Lee, NR, Lehtimaki, T, Lemaitre, RN, Lu, W, Luben, RN, Manichaiku, A, Mannisto, S, Marques-Vidal, P, Monda, KL, Ngwa, JS, Perusse, L, van Rooij, FJA, Xiang, YB, Wen, WQ, Wojczynski, MK, Zhu, JW, Borecki, IB, Bouchard, C, Cai, QY, Cooper, C, Dedoussis, GV, Deloukas, P, Ferrucci, L, Forouhi, NG, Hansen, T, Christiansen, L, Hofman, B, Johansson, I, Jorgensen, T, Karasawa, S, Khaw, KT, Kim, MK, Kristiansson, K, Li, HX, Lin, X, Liu, YM, Lohman, KK, Long, JR, Mikkila, V, Mozaffarian, D, North, K, Pedersen, O, Raitakari, O, Rissanen, H, Tuomilehto, J, van der Schouw, YT, Uitterlinden, A , Zillikens, MC, Franco Duran, OH, Tai, ES, Shu, XO, Siscovick, DS, Toft, U, Verschuren, WMM, Vollenweider, P, Wareham, NJ, Witteman, JCM, Zheng, W, Ridker, PM, Kang, JH, Liang, LM, 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, Sorensen, 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

TY - JOUR

T1 - FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

AU - Qi, QB

AU - Kilpelainen, TO

AU - Downer, MK

AU - Tanaka, T

AU - Smith, CE

AU - Sluijs, Iris

AU - Sonestedtl, E

AU - Chull, AY

AU - Renstrom, F

AU - Lin, XC

AU - Angquist, LH

AU - Huang, JY

AU - Liu, ZH

AU - Li, YP

AU - Ali, MA

AU - Xu, M

AU - Ahluwalia, TS

AU - Boer, JMA

AU - Chen, P

AU - Daimon, M

AU - Eriksson, J

AU - Perola, M

AU - Friedlander, Y

AU - Gao, YT

AU - Heppe, Denise

AU - Holloway, JW

AU - Houston, DK

AU - Kanoni, S

AU - Kim, YM

AU - Laaksonen, MA

AU - Jaaskelainen, T

AU - Lee, NR

AU - Lehtimaki, T

AU - Lemaitre, RN

AU - Lu, W

AU - Luben, RN

AU - Manichaiku, A

AU - Mannisto, S

AU - Marques-Vidal, P

AU - Monda, KL

AU - Ngwa, JS

AU - Perusse, L

AU - van Rooij, FJA

AU - Xiang, YB

AU - Wen, WQ

AU - Wojczynski, MK

AU - Zhu, JW

AU - Borecki, IB

AU - Bouchard, C

AU - Cai, QY

AU - Cooper, C

AU - Dedoussis, GV

AU - Deloukas, P

AU - Ferrucci, L

AU - Forouhi, NG

AU - Hansen, T

AU - Christiansen, L

AU - Hofman, Bert

AU - Johansson, I

AU - Jorgensen, T

AU - Karasawa, S

AU - Khaw, KT

AU - Kim, MK

AU - Kristiansson, K

AU - Li, HX

AU - Lin, X

AU - Liu, YM

AU - Lohman, KK

AU - Long, JR

AU - Mikkila, V

AU - Mozaffarian, D

AU - North, K

AU - Pedersen, O

AU - Raitakari, O

AU - Rissanen, H

AU - Tuomilehto, J

AU - van der Schouw, YT

AU - Uitterlinden, André

AU - Zillikens, M.C.

AU - Franco Duran, OH

AU - Tai, ES

AU - Shu, XO

AU - Siscovick, DS

AU - Toft, U

AU - Verschuren, WMM

AU - Vollenweider, P

AU - Wareham, NJ

AU - Witteman, JCM

AU - Zheng, W

AU - Ridker, PM

AU - Kang, JH

AU - Liang, LM

AU - Jensen, MK

AU - Curhan, GC

AU - Pasquale, LR

AU - Hunter, DJ

AU - Mohlke, KL

AU - Uusitupa, M

AU - Cupples, LA

AU - Rankinen, T

AU - Orho-Melander, M

AU - Wang, Tianshi

AU - Chasman, DI

AU - Franks, PW

AU - Sorensen, TIA

AU - Hu, FB

AU - Loos, RJF

AU - Nettleton, JA

AU - Qi, L

PY - 2014

Y1 - 2014

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 BM I. 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 x 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 x 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 x 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 x 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 BM I. 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 x 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 x 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 x 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 x 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.

U2 - 10.1093/hmg/ddu411

DO - 10.1093/hmg/ddu411

M3 - Article

SN - 0964-6906

VL - 23

SP - 6961

EP - 6972

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 25

ER -