Genetics of childhood obesity

The current prevalence of childhood overweight and obesity is alarmingly high.
Childhood obesity is associated with considerable health risks and it resists
most currently available treatments. There is a substantial genetic
contribution to obesity. Understanding the genetics of obesity will ultimately
lead to improved treatment and prevention strategies. Large studies are
required to elucidate the genetic pathways and gene-environment interactions
involved in obesity. We propose that variation in genes involved in the
regulation of motivational behaviour and satiety plays a major role in the
development of obesity. We aim to identify these genes using family-based
association and linkage analysis in a large cohort of obese children and
adolescents. Although common obesity is a polygenic trait, obesity displays a
monogenic pattern of inheritance in some families. The most common monogenic
form of obesity is caused by mutations in MC4R. Therefore we plan to perform
mutation analysis of the gene encoding the melanocortin 4 receptor (MC4R) in
this cohort. Several aspects of the role of MC4R mutations in obesity remain
unclear. Our cohort is uniquely suited to study these aspects.

We propose that variation in genes involved in the regulation of motivational
behaviour and satiety plays a major role in the development of obesity. We aim
to identify these genes using family-based association and linkage analysis in
a large cohort of obese children and adolescents.

In addition, we plan to perform mutation analysis of the gene encoding the
melanocortin 4 receptor (MC4R) in our cohort with the aim to study the role of
MC4R mutations in obesity.

We have established a centre for childhood and adolescent obesity. In this
centre, we routinely collect a variety of data for diagnostic and treatment
purposes. These data include anthropometric measures, oral glucose tolerance
tests, endocrinological measures, and information about dietary intake,
physical activity, socio-economic status, and ethnicity. We aim to collect DNA
samples of the patients of our centre and their parents. All samples will be
screened for MC4R mutations. We will study the phenotypic characteristics of
patients with MC4R mutations. If we do not find defects in MC4R in the DNA
sample of a patient, the sample will be stored in our DNA bank for future
candidate gene studies and family based association or linkage studies.

We propose to ask patients and their parents for consent to withdraw blood
samples for our genetic studies. Sampling of the children and adolescents will
be performed simultaneously with blood withdrawal for diagnostic purposes.
Consequently, there is no extra burden for patients. Parents of the patients
will undergo venipuncture once. In the future, this study should lead to
improved treatment methods.