Genetic Dissection of the Pathophysiology of Cardiovascular Risk Factors
: Ahola-Olli Ari
Publisher: University of Turku
: Turku
: 2017
: ISBN 978-951-29-6913-5
: ISBN 978-951-29-6914-2
: http://urn.fi/URN:ISBN:978-951-29-6914-2(external)
: http://urn.fi/URN:ISBN:978-951-29-6914-2(external)
Background: Genome-wide association studies (GWAS) have uncovered a pleth-
ora of biological information behind complex diseases. Findings from the GWAS
and subsequent functional studies can facilitate drug development by identifying
novel drug targets and predicting side-effects.
Aims: This thesis investigates the ability of genome-wide data to reveal potential
mechanisms and treatments for cardiovascular diseases using a gene-environment
interaction study, combined use of mice and human data, and detailed molecular
methods involving intermediate phenotype data.
Participants and methods: This thesis is based on data from The Cardiovascular
Risk Factors in Young Finns Study, the Special Turku Coronary Risk Factor In-
tervention Project, and national FINRISK surveys.
Results: The gene-environment design was able to identify one potential drug tar-
get for lowering LDL-cholesterol levels. The effect of dietary fat on serum LDL-
cholesterol was more pronounced in subjects with rs9364628-TT. Combined anal-
yses of mice and human data were able to identify the melanocortin 1 receptor as
a potential drug target for improving cardiovascular health. By using cytokines as
detailed molecular intermediate phenotypes, we were able to identify 27 loci (17
novel) associated with concentrations of circulating cytokines.
Conclusions: Combined used of animal and human data and use of detailed mo-
lecular intermediate phenotypes can be efficiently used to identify drug targets.
More research is needed to elucidate whether gene-environment studies can be
utilized in drug discovery.