Carrier screening has undergone major changes in recent years as technology made it possible to cost-effectively scan many genes at once. Where this kind of screening was once limited to just a couple of diseases, it is now feasible to offer much broader testing through options like Sema4’s Expanded Carrier Screen.
But along with this technological shift have come many important clinical and ethical questions. Those were the focus of a carrier screening session at the recent Association for Molecular Pathology Annual Meeting & Expo in Baltimore, where Sema4’s Chief Diagnostics Officer Lisa Edelmann spoke about identifying ethnicity, residual risk, and more.
Ethnicity matters in carrier screening for a few reasons. First, Edelmann pointed out, many diseases are understudied in certain ethnic groups. This means that guiding people to carrier screening panels developed for a particular ethnic group might miss diseases that are relevant to that group but have not been studied extensively enough within it. Second, patients often misreport their own ethnicity — sometimes because they are not aware of their genetic ancestry and sometimes because the “check-one box” forms fail to provide consumers from admixed populations the chance to fully represent their ethnicity, Edelmann told attendees.
For both of these situations, expanded carrier screening can offer a better option. By testing as many variants as possible, this kind of screening test gives people a greater likelihood of detecting any red flags than a smaller panel focused on a single ethnic population.
Ethnicity also makes a difference for calculating residual risk from negative results in a carrier screen, Edelmann said. This calculation requires understanding carrier frequency within an ethnic population and the detection rate of the screening test. Ethnicity influences both. Historically, residual risk scores were established based on literature searches, Edelmann noted, but now there are better methods. “Currently we can use a data-driven approach for these residual risk calculations [to move] towards a more accurate representation of risk,” she said.
By incorporating specific variant frequencies from publicly available databases, it is now possible to pinpoint carrier frequency with far greater precision. Patients from ethnic groups that have been understudied in the genomic era are more likely to have variants of uncertain significance detected by carrier screens, so their residual risk will typically be higher than that of patients from better-characterized populations.
Here at Sema4, we believe it is imperative to do everything we can to make carrier screening results accurate and comprehensive for all consumers. That’s why we recently announced the addition of Personalized Residual Risk to our carrier screening tests. This risk score is based on the genetic identification of a customer’s ethnicity — rather than relying on potentially incorrect self-reported information — to make each user’s results and residual risk scores as reliable as possible. Of course, we only report the breakdown of ancestry markers to patients who want to learn their results and who provide informed consent prior to accessing their results in our Sema4 patient portal. In either case, though, they can rest assured that they’ll be getting the most accurate results available today.
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