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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Human Molecular Genetics |
| Vol/bind | 23 |
| Udgave nummer | 25 |
| Sider (fra-til) | 6961-6972 |
| Antal sider | 12 |
| ISSN | 0964-6906 |
| DOI | |
| Status | Udgivet - 7 aug. 2014 |
Adgang til dokumentet
- 10.1093/hmg/ddu411Licens: CC BY-NC-SA
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals. / Qi, Qibin; Oskari Kilpeläinen, Tuomas; Downer, Mary K; Tanaka, Toshiko; Smith, Caren E; Sluijs, Ivonne; Sonestedt, Emily; Chu, Audrey Y; Renström, Frida; Lin, Xiaochen; Angquist, Lars H; Huang, Jinyan; Liu, Zhonghua; Li, Yanping; Asif Ali, Muhammad; Xu, Min; Ahluwalia, Tarun Veer 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; Houston, Denise K; Kanoni, Stavroula; 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; Monda, Keri L; Ngwa, Julius S; Perusse, Louis; 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; Ferrucci, Luigi; Forouhi, Nita G; Hansen, Torben; Christiansen, Lene; Hofman, Albert; Johansson, Ingegerd; Jørgensen, Torben; Karasawa, Shigeru; Khaw, Kay-Tee; Kim, Mi-Kyung; Kristiansson, Kati; Li, Huaixing; Lin, Xu; Liu, Yongmei; Lohman, Kurt K; Long, Jirong; Mikkilä, Vera; Mozaffarian, Dariush; North, Kari; Pedersen, Oluf; Raitakari, Olli; Rissanen, Harri; Tuomilehto, Jaakko; van der Schouw, Yvonne T; Uitterlinden, André G; Carola Zillikens, M; Franco, Oscar H; Shyong Tai, E; Ou Shu, Xiao; Siscovick, David S; Toft, Ulla; Monique Verschuren, W M; 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; Pasquale, Louis R; Hunter, David J; Mohlke, Karen L; Uusitupa, Matti; Adrienne Cupples, L; 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; Qi, Lu.
I: Human Molecular Genetics, Bind 23, Nr. 25, 07.08.2014, s. 6961-6972.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
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: [email protected].
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 -