Effects of the FTO gene and environment on obesity in European children

Childhood obesity is considered to be one of the most serious public health problems of the 21st century. The worldwide prevalence of obesity has increased dramatically over the past three decades and while continuing to rise at a rapid rate, along with increasing levels of childhood obesity, are having a profound effect on healthcare development in many low- and middle-income countries, particularly in urban environments. Longitudinal and cross sectional studies have indicated clear associations between environment and obesity risk. In addition, childhood obesity leads to serious health conditions such as cardiovascular disease, type II diabetes and adulthood obesity. Environmental factors, however, do not seem to explain neither all of the variance in childhood obesity prevalence, nor all the variance in response to intervention studies. Although the human genome has not changed over the years, obesity levels and mortality rates have dramatically increased, thus it becomes more evident that environmental factors such as physical activity or sedentary lifestyle may have a key role in this increase of obesity prevalence. However, since the prevalence of childhood obesity is different in certain geographical areas of the world, it is important to investigate the genetic predisposition in relation to its interaction with environmental influences. Genetic studies have demonstrated a contribution of specific genetic variants to obesity in adults. Additionally, heritability studies of childhood obesity support the idea that genetic predisposition may also be a factor in determining childhood obesity or adiposity. The obesity prevalence research becomes even more complicated by gene-environment interactions, where individuals with different genotypes respond differently in certain environments and therefore it is more challenging to define the actual causes of this health problem. The overall aim of this study was to investigate the interplay between genetic and environmental influences such as physical activity on the predisposition to childhood obesity related traits in the IDEFICS cohort. This thesis focused on European children from eight countries participating in the IDEFICS Study including Germany, Italy, Spain, Cyprus, Estonia, Sweden, Belgium and Hungary aged two to ten. The main objective was to characterize the relative contributions of individual genes, environmental factors and gene-environment interactions to this risk. In doing so, this investigation also allowed comparisons between the different age groups and countries and also possible differences between the two sexes. These findings will add to the existing efforts aimed at finding appropriate treatments and effective preventative intervention programs around Europe. In order to explore how environment and genes interact and whether genes can modulate the development of obesity in children of this European population, a detailed characterization of body composition, physical activity patterns, socio-economic, and genetic factors was performed. The main findings from this thesis were that: (a) age is an important factor when studying childhood obesity as body composition changes in a significant way with age, in both boys and girls. These findings also highlight the fact that various environmental and lifestyle effects 4 © A. C. Koni (2013) related to childhood obesity, such as physical activity (PA), differ between the two sexes and among age groups; (b) physical activity and sedentary behaviours may influence obesity related phenotypes in children of European origin. These associations persist after adjustment for a comprehensive range of potential confounding factors; (c) the Fat Mass Obesity-associated (FTO) gene influences obesity related phenotypes in children of European origin. These associations persist after adjustment for a comprehensive range of potential confounding factors; (d) although there was no Gene*PA interaction, physical activity or inactivity seems to play a role in modulating the genetic predisposition to obesity in children. The findings of this study demonstrate that there was a trend of decreased obesity risk phenotypes in children that were more physically active overall. This observation has important public health value, as the data of this thesis indicate that being physically active may have a protective role in the genetic predisposition to obesity induced by variation in the FTO gene. Further studies into the mechanisms underpinning this effect are needed in order to more effectively develop accurate design, as well as implementation strategies to reduce childhood obesity and for advancing the basic understanding of the mechanisms behind human obesity and its relationship with genetics.