A Response to JAMA Article “DNA-Based Population Screening: Potential Suitability and Important Knowledge Gaps”

A Response to JAMA Article DNA- Based Population Screening: Potential Suitability and Important Knowledge Gaps

Response by: Paldeep Atwal, MD, MBA, FRCP(UK) FACMG, PWNHealth Medical Director & VP of Genetic Services, Robin King, MS, CGC, PWNHealth Director Genetic Operations & Programs 

JAMA Abstract: DNA-Based Population Screening: Potential Suitability and Important Knowledge Gaps | Genetics and Genomics | JAMA

At PWNHealth, the core of our mission is to reduce barriers to medically meaningful testing. Recently, on December 6th, in the Journal of The American Medical Association (JAMA), Michael F. Murray et al shared a viewpoint on DNA-based population screening. The article discussed the limitations of using reported medical history in a routine medical visit for genetic risk screening. Factors included a lack of time to conduct thorough family history intake and limitations in the sensitivity of screening for hereditary risk in this way.  In addition, potential benefits of population screening were reviewed and the case for population-based DNA screening was assessed against five keystone principles used for blood pressure screening for cardiovascular risk. The five principles used for population blood pressure screening are:

  1. Is There Easy Detection of Variation From a Defined Normal?
  2. Can the Clinical Importance of Variants Be Readily Interpreted?
  3. Are Well-Established and Well-Tolerated Interventions Available for Individuals With Pathogenic Variations?
  4. Are There Well-Documented Health Benefits From Interventions?
  5. Is There a Lack of Any More Effective Alternative Methodology for Identifying This Risk?

There are a number of genetic conditions in which all the above questions would receive a clear ‘Yes’ that can be supported by the peer-reviewed medical literature (e.g. hereditary breast and ovarian cancer, lynch syndrome, and familial hypercholesterolemia) and this list is ever increasing. In addition, there are a number of articles showing that current guideline criteria for testing miss a significant portion of individuals with these conditions. The authors also discuss the low frequency of individuals with these conditions at a population level and make the case for larger pilot studies to assess evidence of clinical utility and economic impact.

The trend of who is appropriate to be screened continues to become more inclusive; broader testing with less restrictive criteria. This is reflected in medical society statements, the medical literature, what is happening in clinical practice, and clinical guidelines. At PWN, we aim to stay at the forefront of this trend ensuring that all testing is done in a safe manner, ensuring appropriate actions and follow-up occur, particularly as the scale of this testing continues to increase. Through consumer-initiated genetic testing, we have supported hundreds of individuals who have been identified to have a pathogenic or likely pathogenic DNA variant that leads to significant risk for disease. These individuals are then able to pursue medical interventions to reduce or eliminate that risk for themselves and notify family members of their potential risk for the same condition.