There are many ways that monogenic and polygenic testing differ, and they can be used both separately or in tandem to help guide conversations about genetic risk with patients. Some patients that have already had monogenic testing (such as testing for rare pathogenic mutations like BRCA1/2 or HOXB13) may not understand the utility of polygenic screening, especially if those prior monogenic testing results were unremarkable. A good way of breaking this idea down to its most basic concept is by explaining that monogenic testing generally asks a ‘yes or no’ question that relates only to the patient (“Do you have this rare pathogenic mutation or not?”) and polygenic testing asks a ‘how much’ question that relates to the entire population (“how many of these minor variants do you have in your genes and how does that compare to other people?).
This means that while monogenic testing may answer some of the big questions about risk for disease when it comes to specific and serious genetic mutations, it can often miss the plethora of smaller questions related to more common variants. Think of polygenic testing as a calculator of sorts, adding up these more common genetic variants that monogenic testing misses and presenting a score that explains where the patient falls on a risk spectrum in relation to the rest of the population.
For more information about the clinical implementation of PRS, check out our Ask a GC blog posts here