November 19, 2021 11:51 AM

DNA testing at the doctor’s office

A human genetics experts discusses how these DNA tests might be useful in practice and what cautions remain.

doctor swabs man's mouth with mask and eye glass gear on
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Amazing advances in genetic research mean it’s easier than ever to take a DNA test and find out how susceptible you might be to a variety of diseases.

The next question, though, is even more important: What should be done with that information?

Cristen Willer, Ph.D., said more needs to be figured out, and tested in controlled settings, before these disease-specific polygenic risk scores should be widely deployed in medical clinics.

“However, it’s exciting to imagine, a few years down the line, using precision medicine guided by polygenic risk scores,” she said.

Willer, along with Michael Inouye, Ph.D., from Cambridge University and the University of Melbourne, co-chaired a new perspective from the Polygenic Risk Score Task Force of the International Common Disease Alliance in the journal Nature Medicine. Willer is also a professor of internal medicine, human genetics and computational medicine and bioinformatics at University of Michigan Health, where she leads the Willer Lab.

Here, Willer addresses some of the key points in the discussion about whether to use polygenic risk scores in clinical practice.

How does a polygenic risk score work?

Willer: The idea is that one genetic test that costs less than $50 can provide enough genetic information to come up with risk estimates for many diseases, based on polygenic risk scores.  The genome-wide scoring calculates a single score for each individual based on their personal genetics across the entire genome.  The score assigns weights to each marker based on its importance for that disease, coming up with an estimate for a person’s lifetime genetic risk of developing different diseases - heart diseases, diabetes or breast cancer, for example.

What are the most exciting potential benefits?

Willer: The goal is to get useful information about medical risks that then allow a patient and their medical team to reduce those risks. Ideally, these scores would be used in combination with the other clinical risk assessment tools that are already used, including discussion of lifestyle factors.

"It’s exciting to imagine, a few years down the line, using precision medicine guided by polygenic risk scores. "
Cristen Willer, Ph.D.

This might look like tailored advice, such as recommendations that someone become more active and change how they eat, making an appointment for screening sooner than they would have, or taking a new medication.  However, we still need more data to learn about what behavioral or clinical changes are prompted by a polygenic risk score.

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What are you concerned about?

Willer: Like any medical test, there can be errors. And even with a technically accurate result, it’s risky to use a polygenic risk score alone to make decisions. It takes an expert to evaluate these scores and help the patient understand what they mean and what interventions might be worth trying, in order to mitigate risk.

In addition, I can imagine that getting a scary polygenic risk score result for an untreatable disease might be very stressful. There’s a discussion about whether clinicians should restrict delivery to diseases with treatments to avoid that panic.

What gaps still need to be addressed?

Willer: I have a lot of concerns about equity and bias.

Most genetic research has historically focused on people from a European background, which means polygenic risk scores based on genetic research findings might be less applicable to people from other ancestries. It’s very problematic and raises uncomfortable ethical concerns, because we want this research to help as many people as possible. However, colleagues and I currently have another publication in press that aims to address this and advocates for including more diversity in genetic studies in order to optimize polygenic risk scores.

In addition, it’s important to note that we don’t have the genetic counseling resources in this country to scale to delivering polygenic risk scores to many people. Even if everyone decided they wanted to know this information about their individual disease risks, there are not enough genetic counseling experts to help them through the process.

The International Common Disease Alliance aims to improve prevention, diagnosis, and treatment of common diseases across the world, in part through understanding how genetics can be leveraged for the benefit of everyone.  The alliance’s goal is to serve as a scientific forum to facilitate scientific approaches and collaborative projects to move from genetic maps to understanding biological mechanisms to new medicines. 

Paper cited: “Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps,” Nature Medicine. DOI: 10.1038/s41591-021-01549-6

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