Genetics and Epigenetics of Childhood Adiposity : The Generation R Study

In this thesis we investigated the genetic and epigenetic background of childhood adiposity. The prevelence of overweight and obesity in both adults and children is increasing. Meanwhile, little is known on the exact genetic variants, biological pathways, and mechanisms involved in chilhood overweight and fat deposition. Therefore, we examined whether maternal factors including BMI and weight gain during pregnancy are associated with specific sites of fat storage. We also tried to identify genetic variants associated with childhood BMI using a large scale Genome-wide association analysis (GWAS) and combined the childhood BMI associated genetic variants into genetics risk scores. The risk scores were used to tested for association with childhood growth patterns, general adiposity measures, types of fat deposition, and eating behaviours. Furthermore, we explored epigenetic mechanisms underlying childhood adiposity using epigenome-wide association analysis (EWAS). Findings from this thesis suggest that genetic susceptibility of childhood adiposity already has an effect in the early stages of life. Epigenetic mechanisms may play a role in mediating associations of intrauterine exposures and childhood adiposity outcomes, but need further investigation. The observed associations in this thesis may form the basis of a better understanding of the underlying mechanisms of childhood adiposity.

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