The Responsibility to Recontact Research Participants after Reinterpretation of Genetic and Genomic Research Results

Abstract

The evidence base supporting genetic and genomic sequence-variant interpretations is continuously evolving. An inherent consequence is that a variant's clinical significance might be reinterpreted over time as new evidence emerges regarding its pathogenicity or lack thereof. This raises ethical, legal, and financial issues as to whether there is a responsibility to recontact research participants to provide updates on reinterpretations of variants after the initial analysis. There has been discussion concerning the extent of this obligation in the context of both research and clinical care. Although clinical recommendations have begun to emerge, guidance is lacking on the responsibilities of researchers to inform participants of reinterpreted results. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in November 2018. The workgroup included representatives from the National Society of Genetic Counselors, the Canadian College of Medical Genetics, and the Canadian Association of Genetic Counsellors. The final statement includes twelve position statements that were endorsed or supported by the

Six years’ experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias

“…We noted early that research findings were frequently illuminating in a clinical context, and as a result we routinely inform patients of their DNA findings on follow-up visits, and cautiously interpret these. The advice many years ago from our ethics review board seems to have anticipated the current importance of disclosure of results to research patients [86]. Since LipidSeq's content is restricted to lipid disorders, there is no possibility of identifying secondary or incidental findings, except those related to other dyslipidemias.…”

Reanalysis and Reclassification of Rare Genetic Variants Associated with Inherited Arrhythmogenic Syndromes

“…Therapeutic management can be modified but emotional and psychological impacts may have lasting effects [26]. New genetic information can lend itself to misinterpretation [5], so we recommended discussions with an expert cardiologist in genetics to explain what reclassification entails for each patient, accordingly to recent American Society of Human Genetics recommendations (ASHG) [27]. One key point is that a change in classification does not necessarily change the fact that a case has an IAS.…”

Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial

“…We will report pathogenic or likely pathogenic variants for IR [variants expected to be disease causing, as per the American College of Medical Genetics and Genomics (ACMG) guidelines] 3 33. For cancer-related results, we will report VUS results in addition to pathogenic and likely pathogenic variants, given that VUS may be reclassified and become relevant for participants’ primary indication 33 34…”