The results of a polygenic screening test can help inform your clinical team of a patient’s risk of developing certain diseases, which can be particularly useful in the absence of a documented family history. This is true even if the patient has had unremarkable monogenic testing results in the past, as these tests look for different types of genetic risk markers. Screening for Rare Pathogenic Mutations (RPMs) via monogenic testing will usually identify fewer at-risk patients than polygenic screening.
This is due to the unique methodologies of each test. Monogenic testing "scans" for rare pathogenic mutations in specific genes that are known to be associated with certain conditions. These mutations are usually found in a small portion of the general population. Alternatively, polygenic testing looks at a much larger portion of a patient's genome (up to millions of Single Nucleotide Polymorphisms, or SNPs) and calculates the cumulative effect of many genetic variants that are known to have moderate to modest effect on disease risk. From there, a score will be produced that explains how this risk compares to the general population.
To summarize, monogenic testing by nature looks for rare pathogenic mutations, whereas polygenic screening looks for more common genetic variants. This means that polygenic testing can give reference to a patient’s risk of developing certain diseases on its own, or in conjunction with monogenic testing. Often, when monogenic tests provide an ambiguous or unremarkable result, polygenic testing can provide additional context that can then be used to guide discussions about risk modification. Utilizing polygenic testing as a personalized medicine tool allows healthcare providers to catch more at-risk patients that might fall through the cracks using traditional screening methods alone.