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Diabetes Pathophysiology and Genetics
be extensive. In GWAS, allele frequencies of approximately 300,000– type 2 diabetes are involved at a later stage of the disease (β-cell
500,000 common SNPs across the human genome are compared defect). It is suggested that the shared genetic effect may be
one by one between patients and healthy controls. Although this smaller than we thought, or obesity could simply be a non-genetic
approach successfully identified new type 2 diabetes and obesity risk factor for type 2 diabetes because it provokes insulin
genes, a large part of the GWA data have not yet been analysed to resistance. Discovering more obesity and type 2 diabetes genes will
their full potential. provide a broader insight into the shared disease pathology. n
It is possible that single-locus methods do not reflect the correct
Clara C Elbers is a PhD student in the Complex Genetics
underlying model of association. There is growing evidence that
Section of the Department of Medical Genetics and the
gene–gene and gene–environment interactions contribute to Julius Centre for Health Sciences and Primary Care at
complex diseases rather than single genes.
30
Several models for
the University Medical Centre Utrecht. Her main interest
is the genetics and molecular epidemiology of obesity
epistasis (i.e. gene–gene interactions) have been proposed,
31
and type 2 diabetes. Ms Elbers has an MSc in biology.
including those in which the genes alone have no effect on disease
aetiology but where their interaction modifies disease risk. In
addition, it is likely that genetic variation contributes to disease risk
through complex biological pathways. It is unlikely that the genes Marcel GM Wolfs is a PhD student in the Department of
involved in these pathways will be picked up using traditional
Medical Biology at the University of Groningen. His PhD
project is on the genetics of type 2 diabetes. Mr Wolfs
single-locus analyses, and different methods will be needed to
has an MSc in cancer genomics and developmental
extract this information from GWA data sets.
32
biology and a BSc in biomedical sciences.
Conclusion
Common obesity and type 2 diabetes share some non-genetic
factors, as both are influenced by diet and physical inactivity. Both
Timon W van Haeften is an Endocrinologist at the
conditions are characterised by insulin resistance, suggesting a University Medical Centre Utrecht. He has performed
shared pathology. However, results from recent GWAS do not point
studies in the fields of insulin secretion, hypoglycaemia
and the genetics of type 2 diabetes. Dr van Haeften is a
towards shared disease susceptibility loci with an increased risk of
member of the Editorial Board of the European Journal
both obesity and type 2 diabetes. of Clinical Investigation.
Currently, it seems that the susceptibility genes for obesity are
involved at the start of the trait (energy imbalance), and those for
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