TY - JOUR

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

T2 - insights from 177 330 individuals

AU - Qi, Qibin

AU - Oskari Kilpeläinen, Tuomas

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 - Angquist, Lars H

AU - Huang, Jinyan

AU - Liu, Zhonghua

AU - Li, Yanping

AU - Asif Ali, Muhammad

AU - Xu, Min

AU - Ahluwalia, Tarun Veer Singh

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 - Carola Zillikens, M

AU - Franco, Oscar H

AU - Shyong Tai, E

AU - Ou Shu, Xiao

AU - Siscovick, David S

AU - Toft, Ulla

AU - Monique Verschuren, W M

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 - Adrienne Cupples, L

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

N1 - © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2014/8/7

Y1 - 2014/8/7

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.

U2 - 10.1093/hmg/ddu411

DO - 10.1093/hmg/ddu411

M3 - Journal article

C2 - 25104851

VL - 23

SP - 6961

EP - 6972

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 25

ER -