Clinical genome sequencing and population preferences for information about ‘incidental’ findings—From medically actionable genes (MAGs) to patient actionable genes (PAGs)

Abstract

Whole genome or exome sequencing is increasingly used in the clinical contexts, and ‘incidental’ findings are generated. There is need for an adequate policy for the reporting of these findings to individuals. Such a policy has been suggested by the American College of Medical Genetics and Genomics (ACMG). We argue that ACMG’s policy is overly paternalistic, and that an adequate policy must take into account population preferences. We conducted a choice based conjoint survey of population preferences for reporting in a representative sample of the Danish population. In a 12 task survey respondents were asked about their preference for reporting in relation to three scenarios with seven different attributes. Of 1200 respondents 66.4% participated. We show that population preferences for reporting differs from ACMG’s recommendations, and suggest a new policy based on both medically and patient actionable genes.

Responsibility, identity, and genomic sequencing: A comparison of published recommendations and patient perspectives on accepting or declining incidental findings

“…While it has been widely acknowledged that the boundaries between "clinically significant" and "clinically actionable" findings within a genomic sequence are often highly uncertain or even malleable (when interpreted in the context of other relevant health data; Knoppers, Joly, Simard, & Durocher, 2006), their very generation raises significant questions around whether or not patients have the right to access them. Studies that have explored the attitudes of researchers, healthcare professionals, patients, and the general public have consistently demonstrated enthusiasm for, and interest in, receiving IFs on the parts of both the general public and genomic medicine patients, highlighting that the latter two groups harbor the most permissive views around the return of unsolicited genomic findings than any other stakeholder group (Bollinger, Scott, Dvoskin, & Kaufman, 2012;Driessnack et al, 2013;Fernandez et al, 2014;Haga, O'Daniel, Tindall, Lipkus, & Agans, 2011;Middleton et al, 2016;Ploug & Holm, 2017;Townsend et al, 2012;Yushak et al, 2016).…”

Valuation of Health and Nonhealth Outcomes from Next-Generation Sequencing: Approaches, Challenges, and Solutions

“…The potential outcomes of SFs include uncovering risk for diseases that may or may not have effective treatment options, availability of early screening strategies for family members, or pharmacogenetic information on response to drugs. The continuing debate is whether patients should be given information on diseases that are not treatable [6][7][8]. This is because patients may value the information absent of effective treatment and improvement in health status.…”

Genomic Sequencing Expansion and Incomplete Penetrance

“…We aim to optimally implement and interpret the genetics so we can apply genetic technologies in the most effective manner for each individual or population. 4,5 Dominant family pedigrees are well recognized, but X-linked pedigrees are important to consider as well. Many X-linked conditions can have variable penetrance also.…”