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DNA-Based Screening, Effective Clinical Care Must Be Combined to Improve Health, ACMG Says

NEW YORK – In a new guideline published on Tuesday in Genetics in Medicine, the American College of Medical Genetics and Genomics (ACMG) provided some practical advice for the use of DNA-based screening to improve population health.

The guidance is specifically focused on issues related to implementation strategies for DNA-based screening, which the ACMG is setting apart from the DNA-based diagnostic testing that has become a larger part of healthcare within the last few decades. In DNA-based diagnostic testing, an individual is offered testing because of a health concern and therefore has an increased chance of a positive genetic test compared to most people.

DNA-based screening, however, is a system of testing that is offered to all patients, in order to identify whether people who were not previously suspected of being at genetic risk of disease might develop such a condition at some point in their life.

"DNA-based screening is clearly capable of making visible some health risks that would otherwise be invisible," first author and Yale School of Medicine researcher Michael Murray said in a statement. "There are long established principles and practices that are relevant to all health screening, and this statement puts this new screening opportunity in the context of these principles and practices in order to help guide any organization seeking to improve health by offering DNA-based screening."

Chief among the ACMG's conclusions was that DNA-based screening must be combined with effective risk-reducing clinical care if it's going to improve population health. In order to do that effectively, the guidelines' authors sketched out a framework of points to consider. First, the screening shouldn't replace a standard-of-care evaluation for people who have a clinical indication that requires assessment with established diagnostic testing. Individuals who need diagnostic testing would not be well served by the limited approach of screening, the authors wrote.

Second, variants of uncertain significance don't constitute a reportable disease risk in screened individuals. Periodic reanalysis of DNA variants using new information, including population database updates and updates to variant classification recommendations, may reclassify these variants and make them interpretable. But if they remain unclassified, they shouldn't be included in screening results, the authors wrote.

Third, DNA-based screening should be linked to opportunities for evidence-based risk-reducing clinical care. The clinical follow-up for this screening should be consistent with best practices outlined by professional societies with appropriate expertise, the guidance noted.

Fourth, organizations involved in DNA-based screening should share outcomes-related data with each other, and deposit the data into public databases such as ClinVar, in order to improve the research community's collective knowledge, so that human health can be improved through this screening, the authors said.

Finally, the guidelines added that the DNA-based screening applications that prove to have beneficial clinical outcomes over time should be made available to entire populations to promote healthcare equity and limit health disparities.

With those points in mind, the ACMG also said that the guidelines will have to evolve over time, as DNA variants are periodic reanalyzed in relevant databases such as ClinVar; disease status in at-risk individuals is periodically clinical reevaluated; the effectiveness of strategies that support the implementation of DNA-based screening and subsequent clinical management is periodically reassessed.

The organization also noted that the guidance focused on DNA-based screening for a limited number of common and well-studied monogenic conditions, but that there are additional potential screening use-cases, such as pharmacogenomics and polygenic risk scores.