Polygenic risk scores (PRSs)
A polygenic risk score (PRS) 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. PRSs are used to estimate an individual’s risk of developing a particular disease or condition.
PRSs are calculated using data from genome-wide association studies (GWAS), which are studies that identify genetic variants that are associated with a particular disease or condition. GWAS have identified millions of genetic variants that are associated with a variety of diseases, including heart disease, cancer, and diabetes.
To calculate a PRS, researchers first identify the genetic variants that are associated with the disease or condition of interest. They then assign a weight to each genetic variant, based on its strength of association with the disease. The PRS is then calculated as the sum of the weighted genetic variants.
PRSs can be used to estimate an individual’s risk of developing a disease or condition, but they should not be used as a definitive diagnosis. PRSs are only a prediction, and they can be affected by other factors, such as environmental factors and lifestyle choices.
The accuracy of PRSs varies depending on the disease or condition. PRSs are generally more accurate for diseases that are caused by a large number of genetic variants. PRSs are also more accurate for diseases that have a clear genetic basis.
PRSs are still a relatively new technology, and there is still much research being done to improve their accuracy and usefulness. However, PRSs have the potential to be a powerful tool for predicting disease risk and for developing new treatments and prevention strategies.
Here are some of the advantages of using PRSs:
- PRSs can be used to identify individuals who are at high risk of developing a disease, even if they do not have any symptoms. This can help to prevent diseases from developing or to catch them early, when they are more treatable.
- PRSs can be used to develop new treatments and prevention strategies. By understanding the genetic basis of diseases, researchers can develop drugs or other interventions that target specific genes or pathways.
- PRSs can be used to personalize medicine. By taking into account an individual’s genetic risk, doctors can tailor treatments to the individual’s specific needs.
Overall, PRSs are a promising new technology with the potential to improve our understanding of diseases and to develop new treatments and prevention strategies. However, it is important to be aware of the limitations of PRSs and to use them responsibly.
PRS can be calculated using whole-genome sequencing (WGS). WGS is a type of genetic testing that sequences the entire genome of an individual. This allows researchers to identify all of the genetic variants that an individual has, including the variants that are associated with diseases.
To calculate a PRS using WGS, researchers first identify the genetic variants that are associated with the disease or condition of interest. They then assign a weight to each genetic variant, based on its strength of association with the disease. The PRS is then calculated as the sum of the weighted genetic variants.
PRSs calculated using WGS are generally more accurate than PRSs calculated using other methods, such as genome-wide association studies (GWAS). This is because WGS allows researchers to identify all of the genetic variants that an individual has, including the rare variants that are not detected by GWAS.
Here are some of the advantages of using WGS to calculate PRSs:
- WGS allows researchers to identify all of the genetic variants that an individual has, including the rare variants that are not detected by GWAS.
- WGS-based PRSs are generally more accurate than PRSs calculated using other methods.
- WGS can be used to calculate PRSs for a wider range of diseases and conditions.
Overall, WGS is a promising new technology that has the potential to improve the accuracy of PRSs. However, more research is needed to understand the clinical utility of WGS-based PRSs and to address the challenges associated with their use.