ACMG: Do Not Use Polygenic Risk Scores for Embryo Selection

^{Image courtesy National Human Genome Research Institute}

The American College of Medical Genetics and Genomics (ACMG) published on March 15 a “Points to Consider” statement on “the clinical application of polygenic risk scores.” The statement includes sensible and somewhat skeptical analyses of issues involved in using a polygenic risk score (PRS) for making decisions in the clinic about the treatment of patients. The first subhead, and Point 1 of the 8-point summary, is: “PRS test results do not provide a diagnosis, instead they provide a statistical prediction of increased clinical risk.” Point 2 notes that a low PRS does not rule out significant risk. Moreover, from Point 6, “there is currently limited evidence to support the use of PRS to guide medical management.” 

The most controversial applications of PRS, however, involve the selection of embryos, and the ACMG took the opportunity to reiterate in Point 8 that:

The ACMG’s position is that preimplantation PRS testing is not yet appropriate for clinical use and should not be offered at this time.

This latest document, which is intended “primarily as an educational resource for medical geneticists and other clinicians,” mentions and implicitly endorses the 2021 ACMG position statement on “Direct-to-consumer prenatal testing for multigenic or polygenic disorders,” which includes:

However, even with the most sophisticated technologies available, genetic studies on complex traits and disease constitute an inexact science and do not identify affected individuals as does testing for monogenic disorders. Rather, it only assesses the risk for developing a disorder. … the ACMG is of the opinion that prenatal testing for disorders that exhibit multigenic or polygenic inheritance is not yet appropriate for clinical use and should not be offered as direct-to-consumer testing.

Two more forthcoming ACMG documents will address “the ethical, social, and legal considerations associated with PRS testing for embryos.” That is welcome news, especially if the “social” considerations include analysis of the commercial interests of companies that sell such tests and recommendations for enforceable legal restrictions. The issues here are not just about whether would-be parents understand that PRS can’t really deliver geniuses, they are also and more importantly about the wildly inappropriate marketing promises being made by the handful of fertility clinics and testing companies that are already selling embryo “ranking” services.