Physical activity attenuates the body mass index–increasing influence of genetic variation in the FTO gene
Open accessAbstract
Background Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity.Objective We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active.Design The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models.Results We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals.Conclusions Our results showed that PA attenuates the effect of the FTO rs1121980 genotype on BMI and WC. This observation has important public health implications because we showed that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.
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- Authors
- Vimaleswaran, K. S., Li, S., Zhao, J. H., Luan, J., Bingham, S. A., Khaw, K.-T., Ekelund, U., Wareham, N. J., & Loos, R. J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Loos, Ruth JF
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 90
- Issue
- 2
- Pages
- 425-428
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2101375326
- Cited by
- 202
- References
- 24
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 14 · 2018: 5 · 2017: 14 · 2016: 19 · 2015: 9 · 2014: 15 · 2013: 10 · 2012: 19
- FWCI
- 14.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Cancer Research UK
- British Heart Foundation
- European Commission
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- FTO, physical activity, body mass index, waist circumference, gene-environment interaction, fat mass and obesity-associated gene, lifestyle modification
- MeSH terms
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Adult, Aged, Alleles, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Obesity, Proteins, Genetic Variation, Cohort Studies, Exercise, Body Mass Index, Genetic Predisposition to Disease, Waist Circumference
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