Abstract
BackgroundOur aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4.MethodsThe HUNT study comprises health information on the population of Nord-Trøndelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI ≥ 35 kg/m2) in the third survey, HUNT3 (2006–08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995–97).ResultsCross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20–40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive.ConclusionsIn a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity.
Highlights
It is well recognized that both genetic and non-genetic factors are operative in the development and persistence of obesity
We observed larger genetic effects among physically inactive compared to active individuals
Lifestyle modification of FTO and MC4R effects on obesity researchers may apply for access to these data here: http://www.ntnu.edu/hunt/data
Summary
It is well recognized that both genetic and non-genetic factors are operative in the development and persistence of obesity. Given the primacy of FTO, the minor-allele exerts only modest effects in most studies. It is possible that interactions with other factors may under some conditions lead to an increase (or decrease) in effects. Whether the impact of FTO on obesity is modified by lifestyle factors, such as diet, physical activity and smoking has only been partly elucidated. Gene-environment interactions should be tested in relation to age and gender, something that has so far only been rarely done. Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4
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