Interaction Between LDL Cholesterol and PRS May Predict Heart Attack Risk

Allelica, a leading genomics software company specializing in the development of polygenic risk scores (PRS) for personalized medicine, today announced the publication of a study in Circulation (Vol. 143, number 10) showing that the effect of LDL cholesterol on a person’s risk of having a heart attack depends on their genes.

Using Allelica’s proprietary PRS analysis software, data showed that combining information about an individual’s genetic risk for a heart attack with their LDL level helps determine who is most at risk for a stroke. heart disease, including those potentially in need of treatment with statins or PCSK9 inhibitors.

The PRS has also been able to identify people eligible for therapeutic intervention based on current guidelines, which do not include polygenic risk, but are in fact at low risk of heart attack based on their genes. and their LDL levels, which could potentially prevent treatment. A PRS is a measure of a person’s risk of disease based on their genes and relies on the combination of the effects of a large number of genetic variants across the genome.

By demonstrating that an individual’s risk of heart attack depends on an interaction between LDL cholesterol and PRS, Allelica’s research suggests that the assessment of LDL cholesterol per se, as is currently the case, is at best inaccurate and at worst potentially dangerous for those over 10 years old. % of the entire primary prevention population that has a high PRS and yet invisible to current assessments of non-genetic risks.

Our research shows that knowing traditional risk factors is not enough to accurately assess a person’s risk for a heart attack. You also need to know their genetic risk. The optimal level of LDL cholesterol needed to have a normal risk of heart attack differs depending on your polygenic predisposition to heart attack. “

Dr George Busby, Company Director, Allelica

Allelica has developed digital tools to estimate an individual’s PRS for coronary heart disease (CAD). The PRS is based on the latest bioinformatics technology as well as genetic data from around 408,000 people from the UK Biobank.

The study published in Circulation showed that people with both average LDL levels (130-160 mg / dL) and high PRS have an equivalent risk of suffering a heart attack as people with high cholesterol. (> 190 mg / dL) and average PRS. People with high cholesterol are usually prescribed statins, based on current clinical guidelines.

Research has also shown that people with high polygenic scores for CAD can lower their risk of disease to the average population by maintaining optimal LDL levels (<100 mg / dL).

“LDL cholesterol doesn’t affect everyone’s risk of heart attack the same way. Millions of people with average LDL are likely to be at risk for a heart attack because they also have high PRS and would likely need to take lipid lowering drugs. time there are people who take drugs but who may not need them because their genes protect them, ”said Giordano Bottà, PhD, CEO of Allelica. “We were able to identify these distinct groups using our CAD PRS analysis tool, which uses a new score we developed. Our new CAD PRS improves the predictive power of all previously published ones.”

In the next step, Allelica discusses with the health authorities how to integrate its PRS for CAD into the clinical routine. This could have broad implications that support realizing the benefits of precision medicine on a large scale.