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Physical activity and the association of common FTO gene variants with body mass index and obesity.

ABSTRACT: Common FTO (fat mass and obesity associated) gene variants have recently been associated with body mass index (BMI) and obesity in several large studies. The role of lifestyle factors (such as physical activity) in those with an underlying FTO genetic predisposition is unknown.To determine if FTO variants are associated with BMI in Old Order Amish (OOA) individuals, and to further determine whether the detrimental associations of FTO gene variants can be lessened by increased physical activity, a total of 704 healthy OOA adults were selected from the Heredity and Phenotype Intervention (HAPI) Heart Study, an investigation of gene x environment interactions in cardiovascular disease, for whom objective quantified physical activity measurements were available and for whom 92 single-nucleotide polymorphisms (SNPs) in FTO were genotyped.Twenty-six FTO SNPs were associated with BMI (P = .04 to <.001), including rs1477196 (P < .001) and rs1861868 (P < .001), 2 SNPs in moderate linkage disequilibrium in the OOA (D' = 0.82; r(2) = 0.36). Stratified analyses of rs1861868 revealed its association with BMI to be restricted entirely to those subjects with low sex- and age-adjusted physical activity scores (P < .001); in contrast, the SNP had no effect on those with above-average physical activity scores (P = .29), with the genotype x physical activity interaction achieving statistical significance (P = .01). Similar evidence for interaction was also obtained for rs1477196.Our results strongly suggest that the increased risk of obesity owing to genetic susceptibility by FTO variants can be blunted through physical activity. These findings emphasize the important role of physical activity in public health efforts to combat obesity, particularly in genetically susceptible individuals.

SUBMITTER: Rampersaud E

PROVIDER: S-EPMC3635949 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Physical activity and the association of common FTO gene variants with body mass index and obesity.

Rampersaud Evadnie E Mitchell Braxton D BD Pollin Toni I TI Fu Mao M Shen Haiqing H O'Connell Jeffery R JR Ducharme Julie L JL Hines Scott S Sack Paul P Naglieri Rosalie R Shuldiner Alan R AR Snitker Soren S

Archives of internal medicine 20080901 16

<h4>Background</h4>Common FTO (fat mass and obesity associated) gene variants have recently been associated with body mass index (BMI) and obesity in several large studies. The role of lifestyle factors (such as physical activity) in those with an underlying FTO genetic predisposition is unknown.<h4>Methods</h4>To determine if FTO variants are associated with BMI in Old Order Amish (OOA) individuals, and to further determine whether the detrimental associations of FTO gene variants can be lessen ...[more]

PMID: 18779467

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Project description:To evaluate the associations between six single-nucleotide polymorphisms (SNPs) in intron 1 of FTO and body mass index (BMI), a case-control association study of 2314 unrelated Mexican-Mestizo adult subjects was performed. The association between each SNP and BMI was tested using logistic and linear regression adjusted for age, gender, and ancestry and assuming additive, recessive, and dominant effects of the minor allele. Association analysis after BMI stratification showed that all five FTO SNPs (rs1121980, rs17817449, rs3751812, rs9930506, and rs17817449), were significantly associated with obesity class II/III under an additive model (P<0.05). Interestingly, we also documented a genetic model-dependent influence of gender on the effect of FTO variants on increased BMI. Two SNPs were specifically associated in males under a dominant model, while the remainder were associated with females under additive and recessive models (P<0.05). The SNP rs9930506 showed the highest increased in obesity risk in females (odds ratio = 4.4). Linear regression using BMI as a continuous trait also revealed differential FTO SNP contributions. Homozygous individuals for the risk alleles of rs17817449, rs3751812, and rs9930506 were on average 2.18 kg/m(2) heavier than homozygous for the wild-type alleles; rs1121980 and rs8044769 showed significant but less-strong effects on BMI (1.54 kg/m(2) and 0.9 kg/m(2), respectively). Remarkably, rs9930506 also exhibited positive interactions with age and BMI in a gender-dependent manner. Women carrying the minor allele of this variant have a significant increase in BMI by year (0.42 kg/m(2), P = 1.17 x 10(-10)). Linear regression haplotype analysis under an additive model, confirmed that the TGTGC haplotype harboring all five minor alleles, increased the BMI of carriers by 2.36 kg/m(2) (P = 1.15 x 10(-5)). Our data suggest that FTO SNPs make differential contributions to obesity risk and support the hypothesis that gender differences in the mechanisms involving these variants may contribute to disease development.

Project description:ImportanceThe Physical Activity Guidelines Advisory Committee Scientific Report identified important research gaps to inform future guidance for adolescents, including limited evidence on the importance of sedentary behaviors (screen time) and their interactions with physical activity for adolescent health outcomes, including overweight and obesity.ObjectiveTo identify the independent associations of physical activity and screen time categories, and the interactions between physical activity and screen time categories, with body mass index (BMI) and overweight and obesity in adolescents.Design, setting, and participantsThis cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) Study collected from September 10, 2018, to September 29, 2020. Data were analyzed from July 8 to December 20, 2022. A total of 5797 adolescents aged 10 to 14 years from 21 racially and ethnically diverse study sites across the US were included in the analysis.ExposuresCategories of total step count per day (with 1000 to 6000 steps per day indicating low, >6000 to 12 000 steps per day indicating medium, and >12 000 steps per day indicating high), as measured by a wearable digital device (Fitbit), and categories of self-reported screen time hours per day (with 0 to 4 hours per day indicating low, >4 to 8 hours per day indicating medium, and >8 hours per day indicating high).Main outcomes and measuresParticipant BMI was calculated as weight in kilograms divided by height in meters squared and converted into sex- and age-specific percentiles in accordance with the Centers for Disease Control and Prevention growth curves and definitions. Individuals were classified as having overweight or obesity if their BMI was in the 85th percentile or higher for sex and age.ResultsAmong 5797 adolescents included in the analytic sample, 50.4% were male, 61.0% were White, 35.0% had overweight or obesity, and the mean (SD) age was 12.0 (0.6) years. Mean (SD) reported screen time use was 6.5 (5.4) hours per day, and mean (SD) overall step count was 9246.6 (3111.3) steps per day. In models including both screen time and step count, medium (risk ratio [RR], 1.24; 95% CI, 1.12-1.37) and high (RR, 1.29; 95% CI, 1.16-1.44) screen time categories were associated with higher overweight or obesity risk compared with the low screen time category. Medium (RR, 1.19; 95% CI, 1.06-1.35) and low (RR, 1.30; 95% CI, 1.11-1.51) step count categories were associated with higher overweight or obesity risk compared with the high step count category. Evidence of effect modification between screen time and step count was observed for BMI percentile. For instance, among adolescents with low screen use, medium step count was associated with a 1.55 higher BMI percentile, and low step count was associated with a 7.48 higher BMI percentile. However, among those with high screen use, step count categories did not significantly change the association with higher BMI percentile (low step count: 8.79 higher BMI percentile; medium step count: 8.76 higher BMI percentile; high step count: 8.26 higher BMI percentile).Conclusions and relevanceIn this cross-sectional study, a combination of low screen time and high step count was associated with lower BMI percentile in adolescents. These results suggest that high step count may not offset higher overweight or obesity risk for adolescents with high screen time, and low screen time may not offset higher overweight or obesity risk for adolescents with low step count. These findings addressed several research gaps identified by the Physical Activity Guidelines Advisory Committee Scientific Report and may be used to inform future screen time and physical activity guidance for adolescents.

Dataset Information

Physical activity and the association of common FTO gene variants with body mass index and obesity.

Publications

Physical activity and the association of common FTO gene variants with body mass index and obesity.

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