The
study was conducted by scientists at the Broad Institute of MIT and Harvard,
Massachusetts General Hospital (MGH), and Harvard Medical School. The team
included Sekar Kathiresan senior author who led the work with first authors
Amit V. Khera, a cardiologist at MGH and junior faculty member in Kathiresan's
lab, and Mark Chaffin, a computational biologist also in Kathiresan's lab.
‘Polygenic risk screening identifies persons at risk of developing heart disease or cancer much before symptoms appear; starting suitable preventive measures early can significantly reduce the risk’
The
study findings have been published in
Nature Genetics
According
to senior author Sekar Kathiresan, an institute member and director of the
Cardiovascular Disease Initiative at the Broad Institute, as well as director
of the Center for Genomic Medicine at MGH and a professor of medicine at
Harvard Medical School, "We've known for long time that there are people
out there at high risk for disease based just on their overall genetic
variation. Now, we're able to measure that risk using genomic data in a meaningful
way. From a public health perspective, we need to identify these higher-risk
segments of the population so we can provide appropriate care."
Identifying and
Quantifying Risk of Developing Common but Serious Diseases
- The study team first collected
information from earlier genomic studies that have linked genetic
alterations to specific diseases and identified various genetic variants
associated with five common but potentially serious conditions like coronary artery disease, breast
cancer, atrial fibrillation, type 2 diabetes and inflammatory bowel
disease.
- For each disease, they devised an
algorithm (series of steps) combining information from all the known
variants (most of which when present alone have little or no influence in
increasing risk but do so in combination) that would calculate disease
risk and give a single number, namely the polygenic risk score
- Based on a
person's polygenic risk score for a particular disease, it is
possible to predict the person's chances of developing the disease later in life
- The team
validated the polygenic risk score algorithm by testing on data of over
400,000 individuals in the UK Biobank, an exhaustive database of genomic
and clinical information from persons of British origin
- Interestingly,
persons with high polygenic risk score for heart disease did not show any
warning signs or symptoms such as hypertension or high
cholesterol, which are currently
standard parameters that are measured to identify heart disease risk in
the clinic. Thus it predicts risk much earlier even before patient shown
has any symptoms.
According to Khera, "These individuals, who are at
several times the normal risk for having a heart attack just because of the
additive effects of many variations, are mostly flying under the radar,"
he explained. "If they came into my clinical practice, I wouldn't be able
to pick them out as high risk with our standard metrics. There's a real need to
identify these cases so we can target screening and treatments more
effectively, and this approach gives us a potential way forward."
Polygenic
Risk Scores for Common Diseases in the Study
- Among the volunteers in the UK
Biobank dataset, 8 percent were more than thrice as likely to develop
heart disease according to their risk score
- Only 0.8 percent of individuals with
very low polygenic risk scores had coronary artery disease, as opposed to
11 percent for the people with high polygenic risk scores
- 1.5 percent of individuals in the UK
Biobank database had more than triple the risk of developing breast cancer.
- Persons with the highest polygenic
risk scores had five times the
risk of breast cancer; 19 percent of persons with top scores had breast
cancer, as compared to about 4 percent of those with lower scores.
- Similarly polygenic risk score for
atrial fibrillation, type 2 diabetes and inflammatory bowel disease were
obtained and validated
Thus the study suggests that a higher polygenic risk
score is associated with an increased risk of developing the disease compared
to a lower score in a given population
Scope
of Study
If a disease is prevalent in a given population and
has well-defined genetic associations,
polygenic risk scoring
could be incorporated in clinical practice to identify persons at risk . When this is followed by suitable
intervention measures and treatments much before
symptoms appear, it can reduce the risk and improve the outcome for the patient.
Future
Research in This Subject
- Current study is based on data from
persons of European descent; larger studies to include other racial groups are needed to widen
the application of the polygenic risk screening to more populations
- Similar research projects that
gather data on genetic variants and disease associations and validating
the results with reference biobanks are necessary to develop polygenic risk scores for more diseases
In conclusion, some day in the foreseeable future it
may be possible to measure a person's polygenic risk score to predict risk of
getting a specific disease, much like we currently measure a person's blood
glucose or cholesterol.
References : - Amit V. Khera, Mark Chaffin, Krishna G. Aragam, Mary E. Haas, Carolina Roselli, Seung Hoan Choi, Pradeep Natarajan, Eric S. Lander, Steven A. Lubitz, Patrick T. Ellinor & Sekar Kathiresan., "Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations" (2018) Nature Genetics
Source: Medindia
