CLINICAL CONVERSATIONS DR. MCNALLY: Typically, three types of answers can be attained with genetic testing. Genetic testing results are interpreted as pathogenic or likely-pathogenic mutations. Sometimes the result is benign, and this type of genetic result is not included on the test report. But then we have a middle area, a gray zone, which we call ‘variants of uncertain significance’. We can see this type of result in anyone, but those from non-Caucasian backgrounds have an increased chance of getting this type of result. I think it’s important for clinicians who might be working with a variant of uncertain significance result, to work a little bit harder with that patient and that family to try to interpret that result in a better way. That often includes getting clinical information from family members to figure out who else has that disease and then making sure that they get tested. It is also really important to work with a genetic counselor to determine whether that variant is actually pathogenic or non-pathogenic. So, when interpreting a variant, you may have to work a little harder to get to a conclusion. Additionally, the availability of large databases, including large publicly-accessible data, contain genetic testing results. This type of information really helps in the interpretation of these results. In the last few years, the large genetic testing companies have generally made all their data available through these databases. That has helped us to improve the quality of the interpretation across all populations. CARDIOMETABOLIC CHRONICLE: In the future, how do you envision the role of genetic testing and even polygenic risk scores in the care for patients with the cardiometabolic disease? DR. MCNALLY: I think we’ll probably see some increase in genetic risk scores and polygenic risk scores. Cost is much less of a barrier, with high throughput technologies reducing costs. I think in some settings what we will see is a blending of the tests with gene panels integrated with polygenic risk scores. If we imagine a world where the cost of testing is $50-100, many people would choose this. Of course, it depends what you get for that price, but ancestry testing has already shown us that people are interested in this information. One could envision doing this type of testing fairly early in life, of course on a voluntary basis, and knowing some degree of lifetime risk of different diseases. We have seen that having this genetic information has empowered a lot of patients and their family members to personally manage their daily lifestyles, for instance, including exercise and suitable diet as part of their chronic disease management. The data can be incredibly empowering for people and I think that’s what we will see going forward.
22 www.cardiometabolichealth.org
NASH Clinical Trials:
An Outlook On Challenges and Advances
