Our white paper describes an analysis of how Polygenic Risk Score (PRS) can be used to identify those at high genetic risk of cardiovascular disease.
The majority of these individuals would be unlikely to be identified through traditional risk metrics, since PRS is orthogonal to conventional risk factors, such as LDL cholesterol or blood pressure.
Because of this, they’re invisible to current classification procedures. So being able to identify the invisible is a key gap that PRS can fill.
But, at Allelica, we also believe that this information is actionable.
This is because a healthy lifestyle can improve parameters used in risk models, mitigating polygenic risk and bringing those individuals with the highest PRS back into line with the population average.
For example, this analysis of the UK Biobank data explored the relationship between cardiovascular disease, genetic risk and lifestyle. The researchers show that poor lifestyle increased risk of heart disease regardless of genetic risk.
This is important for two reasons: the first is that genetics and lifestyle act independently when it comes to assigning an individual’s risk. So they are complementary pieces of information.
Whilst this analysis is based on the UK Biobank dataset, there’s no reason to believe that this isn’t generalisable to other European populations.
The second, more subtle, conclusion is that individuals at high polygenic risk, here identified as being in the top 20% of polygenic risk scores, are not all at high absolute risk of disease.
Those individuals in this high polygenic risk group who followed healthy lifestyles had a lifetime risk of disease that was in line with the average for their population.
Encouragingly, cardiovascular disease isn’t the only disease for which polygenic risk can be mitigated through behavioural change.
Lifetime risk of diabetes, stroke, and dementia also show the same reductions in high polygenic risk groups for those individuals who follow a healthy lifestyle.