FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals
Open accessAbstract
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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Large investigations pooling multiple cohorts have observed main (population) effects of either dietary influences or genes on major cardiometabolic risk factors.
“Large investigations pooling multiple cohorts have observed main (population) effects of either dietary influences or genes on major cardiometabolic risk factors, but evidence for interactions between diet and these genes is uncommon and, more relevantly, magnitudes of such potential interactions are often small.78-83”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [81]
Evidence for interactions between diet and these genes is uncommon.
“Large investigations pooling multiple cohorts have observed main (population) effects of either dietary influences or genes on major cardiometabolic risk factors, but evidence for interactions between diet and these genes is uncommon and, more relevantly, magnitudes of such potential interactions are often small.78-83”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [81]
Magnitudes of such potential gene-diet interactions are often small.
“Large investigations pooling multiple cohorts have observed main (population) effects of either dietary influences or genes on major cardiometabolic risk factors, but evidence for interactions between diet and these genes is uncommon and, more relevantly, magnitudes of such potential interactions are often small.78-83”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [81]
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- Authors
- 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., Boer, J. M. A., Chen, P., Daimon, M., Eriksson, J., Perola, M., Friedlander, Y., Gao, Y.-T., Heppe, D. H. M., Holloway, J. W., Houston, D. K., Kanoni, S., Kim, Y.-M., Laaksonen, M. A., Jääskeläinen, T., Lee, N. R., Lehtimäki, T., Lemaitre, R. N., Lu, W., Luben, R. N., Manichaikul, A., Männistö, S., Marques-Vidal, P., Monda, K. L., Ngwa, J. S., Perusse, L., van Rooij, F. J. A., Xiang, Y.-B., Wen, W., Wojczynski, M. K., Zhu, J., Borecki, I. B., Bouchard, C., Cai, Q., Cooper, C., Dedoussis, G. V., Deloukas, P., Ferrucci, L., Forouhi, N. G., Hansen, T., Christiansen, L., Hofman, A., Johansson, I., Jørgensen, T., Karasawa, S., Khaw, K.-T., Kim, M.-K., Kristiansson, K., Li, H., Lin, X., Liu, Y., Lohman, K. K., Long, J., Mikkilä, V., Mozaffarian, D., North, K., Pedersen, O., Raitakari, O., Rissanen, H., Tuomilehto, J., van der Schouw, Y. T., Uitterlinden, A. G., Zillikens, M. C., Franco, O. H., Shyong Tai, E., Ou Shu, X., Siscovick, D. S., Toft, U., Verschuren, W. M. M., Vollenweider, P., Wareham, N. J., Witteman, J. C. M., Zheng, W., Ridker, P. M., Kang, J. H., Liang, L., Jensen, M. K., Curhan, G. C., Pasquale, L. R., Hunter, D. J., Mohlke, K. L., Uusitupa, M., Cupples, L. A., Rankinen, T., Orho-Melander, M., Wang, T., Chasman, D. I., Franks, P. W., Sørensen, T. I. A., Hu, F. B., Loos, R. J. F., Nettleton, J. A., & Qi, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- University of Cambridge (GB)
- National Institute on Aging (US)
- Tufts University (US)
- University Medical Center Utrecht (NL)
- Lund University (SE)
- Harvard University (US)
- Frederiksberg Hospital (DK)
- Shanghai Jiao Tong University (CN)
- University of Copenhagen (DK)
- National Institute for Public Health and the Environment (NL)
- Yamagata University (JP)
- Finnish Institute for Health and Welfare (FI)
- Hebrew University of Jerusalem (IL)
- University of Southampton (GB)
- Queen Mary University of London (GB)
- Dong-A University (KR)
- University of Eastern Finland (FI)
- University of San Carlos (PH)
- Fimlab (Finland) (FI)
- University of Virginia (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Amgen (United States) (US)
- Boston University (US)
- Vanderbilt University (US)
- Washington University in St. Louis (US)
- Chinese Academy of Sciences (CN)
- Pennington Biomedical Research Center (US)
- Southampton General Hospital (GB)
- Harokopio University of Athens (GR)
- Novo Nordisk Foundation Center for Basic Metabolic Research (DK)
- University of Southern Denmark (DK)
- Glostrup Hospital (DK)
- Hanyang University (KR)
- Wake Forest University Health Sciences (US)
- University of Helsinki (FI)
- University of Turku (FI)
- Universität für Weiterbildung Krems (AT)
- Erasmus MC (NL)
- Netherlands Consortium for Healthy Ageing (NL)
- University of Washington (US)
- Massachusetts Eye and Ear Infirmary (US)
- University of North Carolina at Chapel Hill (US)
- Brigham and Women's Hospital (US)
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Qi, Lu
- ORCID
- Qi, Qibin
- 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
- Liu, Zhonghua
- Li, Yanping
- Xu, Min
- Ahluwalia, Tarunveer Singh
- Boer, Jolanda M.A.
- Chen, Peng
- Daimon, Makoto
- Eriksson, Johan
- Perola, Markus
- Friedlander, Yechiel
- Holloway, John W.
- Houston, Denise K.
- Kanoni, Stavroula
- Kim, Yu-Mi
- Laaksonen, Maarit A.
- Jääskeläinen, Tiina
- Lehtimäki, Terho
- Lu, Wei
- Luben, Robert N.
- Manichaikul, Ani
- Männistö, Satu
- Marques-Vidal, Pedro
- Ngwa, Julius S.
- 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
- Johansson, Ingegerd
- Jørgensen, Torben
- Khaw, Kay-Tee
- Kim, Mi-Kyung
- Kristiansson, Kati
- Long, Jirong
- Mozaffarian, Dariush
- North, Kari
- Pedersen, Oluf
- Raitakari, Olli
- Rissanen, Harri
- Tuomilehto, Jaakko
- Uitterlinden, André G.
- Zillikens, M. Carola
- Franco, Oscar H.
- Siscovick, David S.
- Toft, Ulla
- Verschuren, W.M. Monique
- Wareham, Nicholas J.
- Zheng, Wei
- Ridker, Paul M.
- Kang, Jae H.
- Liang, Liming
- Jensen, Majken K.
- Curhan, Gary C.
- Pasquale, Louis R.
- Mohlke, Karen L.
- Uusitupa, Matti
- Cupples, L. Adrienne
- Wang, Tao
- Chasman, Daniel I.
- Franks, Paul W.
- Sørensen, Thorkild I.A.
- Hu, Frank B.
- Loos, Ruth J. F.
- Qi, Lu
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-08-07
- Volume
- 23
- Issue
- 25
- Pages
- 6961-6972
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC4271061
- OpenAlex
- W2164163537
- Cited by
- 167
- References
- 56
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 10 · 2023: 10 · 2022: 12 · 2021: 19 · 2020: 14 · 2019: 15 · 2018: 19 · 2017: 26 · 2016: 15 · 2015: 16 · 2014: 3
- FWCI
- 13.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-sa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- UNC Libraries
- Funders
- Cancer Research UK (14136)
- National Institute for Health and Care Research (NF-SI-0508-10082, NF-SI-0512-10114, NF-SI-0513-10085, NF-SI-0512-10135)
- Novo Nordisk Fonden (NNF14OC0011049)
- National Institutes of Health (5r01ag032098-05, n01hc085082-026, n01hc085081-021, 5r01dk068336-03, n01hc085079-024, 1r01hl120393-01a1, n01hc085083-027, n01hc085080-026, n01hc095169-003, UL1TR000124, n01hc085086-022, 5r01hl087700-03, 5p01dk070756-05, n01hc25195-41-0-1, 5r01hl088215-04, 5p20rr020649-03, n01hc55222-0-0-0, 5r01hl043851-10, n01hc95159-40-0-1)
- U.S. Public Health Service (HHSN 268200625226C)
- Canadian Institutes of Health Research (77652_1, GR-15187)
- Medical Research Council (MC_UU_12015/5, MC_UU_12011/1, MC_UU_12015/1)
- National Institute on Aging (N01‐AG‐6–2101, R01AG032098, AG023629, N01AG62106, N01-AG-62103)
- National Heart, Lung, and Blood Institute (N01-HC-85081, HHSN268201 100012C, R01HL080467, R01HL071205, HHSN268201100007C, N01HC-85083, N01 HC-95159, HHSN2682 01100008C, HL043851, HH-SN-268201100006C, R01HL071252, HHSN268201100011C, HL085144, R01HL085251, R01HL071981, 5R01 HL08770003, HL-105756, HL 45670, R01-HL120393, N01‐HC25195, HL-087652, R01HL071259, N01HC85082, N01 HC85086, R01 HL-59367, R01HL087652, HHSN268201100005C, R01HL103612, HHSN 268200800007C, R01HL071251, N01HC85080, HHSN268201100010C, N02- HL-64278, N01 HC55222, R01HL073168, R01HL071051, HL103612, R01HL071250, R01HL087641, HHSN268201200036C, HL085251, R01HL059367, HHSN26820 1100009C, R21HL126024, HL-073168, HL-071981, R01HL105756, HL080467, 5-R01-HL-08821502, K08HL112845, HL120393, R01HL085144, R01HL071258, R01HL085710, HL-088521, HL34594, HL080295, R01HL117078, R01HL045670, R01HL086694, R01HL034594, R01HL088521, N01-HC85079, N01 HC95169)
- National Human Genome Research Institute (U01HG004399, U01HG004402, U01HG004728, HHSN268200782096C)
- National Eye Institute (R01EY015473, EY 015473)
- National Cancer Institute (R01-CA82729, R01CA092585, CA-49449, R01CA064277, CA-87969, R37CA070867, CA055075, R01CA148667, P01CA087969, R01CA124558, R01CA082729, UM1CA173640, U54CA155626, CA 047988, R01CA047988, R01CA122364, UM1CA182910, P30CA016086)
- Fogarty International Center (R01TW008288, TW05596, TW008288, R01TW005596)
- National Institute of Diabetes and Digestive and Kidney Diseases (5R01 DK06833603, R01DK091718, DK063491, DK080140, DK091718, R01DK078150, 5P30 DK46200, DK078150, R01DK089256, R01DK058845, DK-70756, R01DK075681, P30DK046200, K24DK080140, 5-R01-DK-07568102, DK56350, DK58845, P30DK063491, P30DK056350, DK46200.)
- National Institute of Environmental Health Sciences (ES 10126, P30ES010126)
- National Center for Research Resources (UL1RR025005, RR20649, RR024156)
- National Center for Advancing Translational Sciences
- National Institute on Minority Health and Health Disparities (263MD9164, 263MD 821336, R01MD009164)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- FTO, rs9939609, obesity, body mass index, protein intake, macronutrient intake, energy intake, gene-diet interaction, genetic susceptibility to obesity, adiposity
- MeSH terms
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Adult, Aged, Alleles, Black or African American, Energy Intake, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Female, Gene Frequency, Humans, Male, Middle Aged, Obesity, Proteins, Body Mass Index, Polymorphism, Single Nucleotide, White People, Asian People
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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