Polygenic risk scores

What are polygenic risk scores?

Polygenic risk scores (PRS) represent the total number of genetic variants that an individual has to assess their heritable risk of developing a particular disease. It is a number that summarizes the estimated effect of many genetic variants on an individual's phenotype, typically calculated as a weighted sum of trait-associated alleles.

Why are polygenic risk scores important?

Combining polygenic risk scores with other factors that affect disease risk can give a better idea of how likely you are to get a specific disease than considering either alone. Knowing how likely you are to get a disease can help you take steps to prevent it or find it earlier when it is easier to treat. Polygenic risk scores can also be combined with other factors to help predict how a disease will progress and how well you will respond to treatment.

What is a genomic variant?

A genomic variant refers to the difference between the near-identical DNA sequences that occur at certain positions on the sequence. Some variants may increase the risk of developing diseases, reduce such risk, or have no effect on disease risk.

Many inherited diseases can be traced to variants in a single gene. These are called single-gene diseases. One such example is cystic fibrosis.

Complex diseases occur as a result of many genomic variants, paired with environmental influences (such as diet, sleep, stress, and smoking habits). They are also called polygenic diseases. One such example is coronary artery disease.

How are polygenic risk scores calculated?

Scientists identify genomic variants associated with complex diseases by comparing the genomes of individuals with and without those diseases.

The enormous amount of genomic data now available allows the, to calculate which variants tend to be found more frequently in groups of people with a given disease. There can be hundreds or even thousands of variants per disease.

They then use computational and statistical methods to estimate how the collection of a person’s variants affects their risk for a certain disease.

How can polygenic risk scores be interpreted?

A polygenic risk score can only explain the relative risk for a disease. The data used for generating a polygenic risk score comes from large-scale genomic studies. These studies find genomic variants by comparing groups with a certain disease (cases) to a similar group without the disease (controls). It tells you how a person’s risk compares to others with a different genetic constitution. However, they do not provide a baseline or timeframe for the progression of a disease.

Each polygenic risk score can be put on a bell curve distribution. Most people will find their scores to be in the middle, indicating average risk for developing a disease. Others may find themselves on the tail ends, putting them at either low or high risk. People with scores on the high-risk portion of the spectrum may benefit from discussions about this risk with their physicians and genetic counselors for further health assessments.