Article

FTO genotype and adiposity in children: physical activity levels influence the effect of the risk genotype in adolescent males.

Integrative and Systems Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
European journal of human genetics: EJHG (Impact Factor: 3.56). 12/2010; 18(12):1339-43. DOI: 10.1038/ejhg.2010.131
Source: PubMed

ABSTRACT Studies of the fat mass and obesity-associated (FTO) gene provide compelling evidence of genetic variation in the general population that influences fat levels and obesity risk. Studies of the interaction between genetic and environmental factors such as physical activity (PA) will promote the understanding of how lifestyle can modulate genetic contributions to obesity. In this study, we investigated the effect of FTO genotype, and interactions with PA or energy intake, in young children and adolescents. In all, 1-5-year-old children from the Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) study (N=1980) and 11-18-year-old Greek adolescents (N=949) were measured for adiposity-related phenotypes and genotyped at the FTO single-nucleotide polymorphism (SNP) marker, rs17817449. Adolescents were classified as physically active or inactive based on self-reported levels of PA. In adolescents, FTO genotype influenced weight (P=0.001) and BMI (P=0.007). There was also a significant SNP(*)PA(*)gender interaction (P=0.028) on BMI, which reflected the association between FTO genotype and BMI in males (P=0.016), but not females (P=0.15), and significant SNP(*)PA interaction in males (P=0.007), but not females (P=0.74). The FTO genotype effect was more pronounced in inactive than active males. Inactive males homozygous for the G allele had a mean BMI 3 kg/m(2) higher than T carriers (P=0.008). In the GENESIS study, no significant association between FTO genotype and adiposity was found. The present findings highlight PA as an important factor modifying the effect of FTO genotype.

0 Bookmarks
 · 
107 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: We aimed to determine if previously identified adult obesity susceptibility loci were associated uniformly with childhood BMI across the BMI distribution. Design and Methods: Children were recruited through the Children's Hospital of Philadelphia (n=7225). Associations between the following loci and BMI were assessed using quantile regression: FTO (rs3751812), MC4R (rs12970134), TMEM18 (rs2867125), BDNF (rs6265), TNNI3K (rs1514175), NRXN3 (rs10146997), SEC16B (rs10913469), and GNPDA2 (rs13130484). BMI z-score (age and gender adjusted) was modeled as the dependent variable, and genotype risk score (sum of risk alleles carried at the 8 loci) was modeled as the independent variable. Results: Each additional increase in genotype risk score was associated with an increase in BMI z-score at the 5th, 15th, 25th, 50th, 75th, 85th and 95th BMI z-score percentiles by 0.04 (±0.02, p=0.08), 0.07 (±0.01, p=9.58 x 10-7), 0.07 (±0.01, p=1.10 x 10-8), 0.09 (±0.01, p=3.13 x 10-22), 0.11 (±0.01, p=1.35 x 10-25), 0.11 (±0.01, p=1.98 x 10-20), and 0.06 (±0.01, p=2.44 x 10-6), respectively. Each additional increase in genotype risk score was associated with an increase in mean BMI z-score by 0.08 (±0.01, p=4.27 x 10-20). Conclusion: Obesity risk alleles were more strongly associated with increases in BMI z-score at the upper tail compared to the lower tail of the distribution.
    Obesity 02/2013; · 3.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Physical activity has been shown to attenuate the effect of the FTO polymorphism on body weight, and the heritability of body weight in twin and in family studies. The dose-response relationship between activity and the risk for inherited obesity is not well known, particularly for higher doses of vigorous exercise. Such information is needed to best prescribe an exercise dose for obesity prevention in those at risk due to their family history. We therefore analyzed self-reported usual running distance, body mass index (BMI), waist circumference, and mother's and father's adiposity (1 = lean, 2 = normal, 3 = overweight, and 4 = very overweight) from survey data collected on 33,480 male and 14,211 female runners. Age-, education-, and alcohol-adjusted regression analyses were used to estimate the contribution of parental adiposities to the BMI and waist circumferences in runners who ran an average of <3, 3-6, 6-9, ≥ 9 km/day. BMI and waist circumferences of runners who ran <3 km/day were significantly related to their parents adiposity (P<10(-15) and P<10(-11), respectively). These relationships (i.e., kg/m(2) or cm per increment in parental adiposity) diminished significantly with increasing running distance for both BMI (inheritance×exercise interaction, males: P<10(-10); females: P<10(-5)) and waist circumference (inheritance × exercise interaction, males: P<10(-9); females: P = 0.004). Compared to <3 km/day, the parental contribution to runners who averaged ≥ 9 km/day was diminished by 48% for male BMI, 58% for female BMI, 55% for male waist circumference, and 58% for female waist circumference. These results could not be attributed to self-selection. Exceeding the minimum exercise dose currently recommended for general health benefits (energy equivalent to running 2-3 km/day) may substantially diminish the risk for inherited obesity. The results are consistent with other research suggesting the physical activity dose required to prevent unhealthy weight gain is greater than that recommended for other health benefits.
    PLoS ONE 01/2012; 7(2):e31436. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity and related complications are major health burdens. Almost 700 million adults are currently obese globally and the prevalence is predicted to rise towards 2030. The sudden change of lifestyle with physical inactivity and excessive calorie intake undoubtedly have a major part of the epidemic development; however, some individuals seem to be more prone to be affected by an unhealthy lifestyle than others. Hence, genetic predisposition also has an essential role in determining disease susceptibility and response to lifestyle factors. Since the introduction of genome-wide association studies (GWAS), the success of identifying obesity susceptibility variants have increased, and a total of 32 variants have been identified associating genome-wide significantly with body mass index (BMI) and 18 with measures of fat distribution during four overall obesity GWAS waves. However, the immediate success of the GWAS approach has eased off, but the proportion of explained variance for BMI by the identified obesity variants remains low. This review suggests and discusses new initiatives to take GWAS of obesity to the next level, including gene-environment interactions as modulating/masking factors, low-frequent or rare variants and ways to address such analyses, and finally reflections about the applicability of epigenetic modifications when elucidating the genetic background of obesity.
    Nutrition & Diabetes 01/2012; 2:e37.

Full-text (2 Sources)

View
26 Downloads
Available from
May 20, 2014