Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene

MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge CB2 0QQ, United Kingdom.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 06/2009; 90(2):425-8. DOI: 10.3945/ajcn.2009.27652
Source: PubMed


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.
We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active.
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.
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.
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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    • "Given the current state of scientific research, these behavioral and environmental factors are modifiable by the individual or society, while the biological factors, such as genetic predispositions, are less subject to modification. However, it is important to acknowledge that the effect of a genetic susceptibility to being overweight or obese is also modifiable by behavioral factors such as a physically active lifestyle [12]. "
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    ABSTRACT: Previous studies have focused on weight maintenance following weight loss, i.e. secondary weight maintenance (SWM). The long-term results of SWM have been rather modest and it has been suggested that preventing initial weight gain, i.e. primary weight maintenance (PWM), may be more successful. Therefore, developing a prevention strategy focused on PWM, enabling normal weight or overweight individuals to maintain their weight, would be of great interest. The aim of this study was to identify attitudes, strategies, and behaviors that are predictive of PWM in different age, sex and BMI groups in Northern Sweden. A questionnaire was mailed to 3497 individuals in a Swedish population that had two measured weights taken ten years apart, as participants in the Vasterbotten Intervention Programme. Subjects were between 41--63 years of age at the time of the survey, had a baseline BMI of 20--30, and a ten year percent change in BMI greater than -3%. The respondents were divided into twelve subgroups based on baseline age (30, 40 and 50), sex and BMI (normal weight and overweight). Analysis of variance (ANOVA), correlation, and linear regression were performed to identify independent predictors of PWM. Of the 166 predictors tested, 152 (91.6%) were predictive of PWM in at least one subgroup. However, only 7 of these 152 variables (4.6%) were significant in 6 subgroups or more. The number of significant predictors of PWM was higher for male (35.8) than female (27.5) subgroups (p=0.044). There was a tendency (non significant) for normal weight subgroups to have a higher number of predictors (35.3) than overweight subgroups (28.0). Adjusted R-squared values ranged from 0.1 to 0.420. The large number of PWM predictors identified, and accompanying high R-squared values, provide a promising first step towards the development of PWM interventions. The large disparity in the pattern of significant variables between subgroups suggests that these interventions should be tailored to the person's demographic (age, sex and BMI). The next steps should be directed towards evaluation of these predictors for causal potential.
    Nutrition Journal 07/2013; 12(1):97. DOI:10.1186/1475-2891-12-97 · 2.60 Impact Factor
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    • "Consistent with our result, recent report revealed that FTO rs9939609 polymorphism did not show a significant effect on antipsychotic-associated weight gain.19) It is suggested that the medications and lifestyle modifications such as physical activity or diet could overcome the genetic predisposition to obesity in patients with schizophrenia.20,21) As most of our patients were hospitalized for long periods and their food intake and exercise were managed according to the institution's rule, environmental interventions could overcome the genetic susceptibility conferred by the FTO genotype. "
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    ABSTRACT: Fat-mass and obesity-associated (FTO) gene is known to be involved in the pathophysiology of obesity and a single-nucleotide polymorphism (SNP) rs9939609 of FTO gene is repeatedly confirmed to be associated with body mass index (BMI) and obesity. The aim of this study is to elucidate effects of FTO gene polymorphism on BMI in Japanese patients with schizophrenia and healthy subjects. Three hundred fifty one patients with schizophrenia and 342 age- and sex-matched healthy subjects participated in the study. Information on BMI and antipsychotic medication was also collected from patients and healthy subjects. Genotype of the FTO SNP rs9939609 was determined by TaqMan SNP Genotyping Assays. There was no significant difference in BMI between patients and healthy subjects. No significant difference in BMI was observed among any medications. We observed no significant difference in rs9939609 allele frequencies between patients and healthy subjects. There was a significant difference in BMI between healthy subjects with risk (AA or TA) genotypes and those with TT genotype. We also observed a significant positive correlation between the number of risk allele (A allele) and BMI in healthy subjects. Our study suggested that FTO rs9939609 polymorphism might have some impacts on the BMI in healthy subjects, but might not have same impacts on the BMI of patients with schizophrenia.
    Clinical Psychopharmacology and Neuroscience 12/2012; 10(3):185-9. DOI:10.9758/cpn.2012.10.3.185
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    • "Twin studies conducted in several populations have found lower heritability of obesity in physically more active individuals [9]–[11]. Similarly on a molecular genetic level, several studies have recently found that physical activity attenuates the effect of the fat mass and obesity associated (FTO) gene and other genetic loci that are associated with body fatness [12]–[15]. In addition, fat and carbohydrate intake has been found to interact with the FTO gene on BMI [16]. "
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    ABSTRACT: There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin and family studies suggest that genetic differences are responsible for the major part of the variation in adiposity within populations. Recent studies show that the genetic effects on body mass index (BMI) may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that the genetic variance of BMI has increased during the obesity epidemic. The data comprised height and weight measurements of 1,474,065 Swedish conscripts at age 18-19 y born between 1951 and 1983. The data were linked to the Swedish Multi-Generation Register and the Swedish Twin Register from which 264,796 full-brother pairs, 1,736 monozygotic (MZ) and 1,961 dizygotic (DZ) twin pairs were identified. The twin pairs were analysed to identify the most parsimonious model for the genetic and environmental contribution to BMI variance. The full-brother pairs were subsequently divided into subgroups by year of birth to investigate trends in the genetic variance of BMI. The twin analysis showed that BMI variation could be explained by additive genetic and environmental factors not shared by co-twins. On the basis of the analyses of the full-siblings, the additive genetic variance of BMI increased from 4.3 [95% CI 4.04-4.53] to 7.9 [95% CI 7.28-8.54] within the study period, as did the unique environmental variance, which increased from 1.4 [95% CI 1.32-1.48] to 2.0 [95% CI 1.89-2.22]. The BMI heritability increased from 75% to 78.8%. The results confirm the hypothesis that the additive genetic variance of BMI has increased strongly during the obesity epidemic. This suggests that the obesogenic environment has enhanced the influence of adiposity related genes.
    PLoS ONE 11/2011; 6(11):e27135. DOI:10.1371/journal.pone.0027135 · 3.23 Impact Factor
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