- Genes associated with cardiometabolic disease (CMD)
- Interaction of genes influences disease pathways
- More number of drug targets for better care
are complex disorders that combine cardiovascular as well as metabolic
disorders. It is important to identify genetic factors associated with these
diseases to aid in screening.
A causative risk factor
increases the incidence of the disease and on including intervention in the
form of dietary supplements, medication or any such treatment procedure, the
risk of the disease is limited. A biomarker is not necessarily associated with
an increase in incidence but it could signal the presence or the future
possible occurrence of the disease. A genetic study will aid in differentiating
between causative risk factor and a non-causative biomarker.
‘Specific genes identified for cardiometabolic risk.’
Studying Risk Factors
It is important to study
risk factors and a notable example for this is the Framingham Heart study that
has been active for the past 60 years. Currently, the grandchildren of the
original study participants are being studied.
Such studies provide a
wealth of knowledge that is used to
- Identify risk factors
- Frame methodologies that lower the risk for the disease
- Identify intervention strategies
Australian data has
shown that there has been an 80% reduction in the incidence of cardiovascular
disease since 1970. This is largely due to the extensive studies carried out about
possible risk factors and the necessary interventional strategies that can
improve the situation.
Genome Wide Association Studies
Genome Wide Association
Studies (GWAS) have found 755 SNP (single nucleotide polymorphisms) spread over
366 independent loci.
Interaction of Genes that Increase the Risk for
Scientists have been
able to identify an interaction of genes in the tissues that increase the risk
for cardiometabolic diseases including pathways that could lead to stroke
or a heart
The study is published
in the Journal Science
and researchers from Icahn School of Medicine at
Mount Sinai, the Karolinska Institutet and Science for Life Laboratory
(SciLifeLab) in Sweden, AstraZeneca and scientists from Tartu University
Hospital in Estonia have collaborated to carry out the research.
Dr. Johan Björkegren who
is the senior author of the study from the Icahn School of Medicine at Mount
Sinai said "By analyzing gene-expression data from multiple tissues in
hundreds of patients with coronary artery disease, we were able to identify
disease-causing genes that either were specific to single tissues or acted
across multiple tissues in networks to cause cardiometabolic diseases."
Dr. Björkegren then
added "Genome-wide association studies (GWAS) have identified thousands of
DNA variants increasing risk for common diseases like CAD. However, while GWAS
was an important first line of investigations of the genetics of CAD, in order
to translate these risk markers into opportunities for new diagnostics and
therapies, we must now move into a new phase of discovery and identify the
genes perturbed by these DNA variants responsible for driving disease
development. Furthermore, we also need to understand in which tissues,
pathways, and molecular networks these disease genes are active. Unraveling
disease-driving genes with their tissue-belonging, as we have started to achieve
using STARNET, will also be a prerequisite for developing precision medicine
with individualized diagnostics and therapies."
STARTNET was started in
2007 by Dr. Björkegren and Arno Ruusalepp. 600 coronary artery disease patients who required
cardiac bypass surgery
in the study while the clinical samples that were collected were
- Vascular Tissue
- Metabolic tissue
The current study is a
part of the STARTNET study. Dr. Oscar Franzén who is the first author of the
study says "One unexpected and thus potentially important finding of the
study was that besides the liver, abdominal fat emerged as a key site for
regulation of blood lipid levels. "For example, a gene called PCSK9, which
is implicated in controlling plasma levels of low-density lipoprotein (LDL)
--the so-called bad
cholesterol--was found to do so by acting in abdominal fat, not in the liver
where blood levels of LDL are mainly regulated." PCSK9 has lately gained
substantial attention as the latest target for lipid-lowering drugs now
reaching the market."
The gene interaction that exists in various
tissue systems is important for understanding the metabolic pathways that lead
to the development of disease. Moreover, it provides new drug targets. As Dr.
Eric Schadt who is the senior co-author points out "We were not only able
to assign a high number of individual genes to DNA markers previously
identified by GWAS but also, and quite unexpectedly, we found that many of
these downstream genes appeared in disease-causal gene regulatory networks that
were shared across tissues and diseases."
- Genetic Insights into Cardiometabolic Risk Factors - (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961996/)
- GWAS as a Driver of Gene Discovery in Cardiometabolic Diseases. - (http://www.ncbi.nlm.nih.gov/pubmed/26596674)