RESEARCH ARTICLE Genetics Professionals’ Perspectives on Reporting Incidental Findings From Clinical Genome-Wide Sequencing Zoe Lohn, 1 * Shelin Adam, 1 Patricia Birch, 1 Anne Townsend, 2 and Jan Friedman 1 1 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada 2 Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, British Columbia, Canada Manuscript Received: 20 June 2012; Manuscript Accepted: 4 November 2012 Whole exome or whole genome analysis using massively parallel sequencing technologies will undoubtedly solve diagnostic dilemmas; however, incidental findings (IF) that may have medical and social implications will also be discovered. While there is consensus in the literature that analytically valid and medically actionable IF should be returned to patients if requested, there is debate regarding the return of other IF. There are currently no guidelines established for managing IF in the clinical context. We therefore distributed an online questionnaire to 496 geneticists and genetic counselors in Canada to explore this unresolved issue, and 210 professionals participated (response rate ¼ 42%). The proportion of respond- ents who indicated that they would return IF to patients depended on the nature of the finding, ranging from 95% for information pertaining to a serious and treatable condition to 12% for information with only social implications (e.g., non- paternity). There was a lack of consensus around the disclosure of certain IF such as genetic carrier status, especially for pediatric patients. The most important considerations identified as impacting IF disclosure included condition-specific factors such as treatment availability, test accuracy, and evidence indi- cating pathogenicity. This is the first study to document the views of geneticists and genetic counselors in Canada towards the disclosure of IF, and represents a step towards evidence-based guidelines for clinical genome-wide sequencing investigations. Ó 2013 Wiley Periodicals, Inc. Key words: incidental finding; whole genome sequencing; whole exome sequencing; clinical context INTRODUCTION Whole genome or whole exome sequencing using massively parallel technologies can uncover variants underlying genetic conditions at an unparalleled cost and efficacy compared to other genetic tech- nologies [Tucker et al., 2009; Ashley et al., 2010; Gonzaga-Jauregui et al., 2012]. In addition, genetic variants will be discovered that may have important medical or social implications that are unre- lated to the indication for testing, called incidental findings (IF) [Kohane et al., 2006; Wolf et al., 2008]. There are currently no guidelines established in Canada for managing IF in the context of clinical sequencing. Whole genome or whole exome sequencing investigations will inevitably discover IF. For example, it is estimated that each human genome contains about 300 single nucleotide variants that are predicted to impact protein function, 100 of which are loss-of- function variants [MacArthur et al., 2012; Tennessen et al., 2012]. By 2015, it is estimated that there will be more than 15,000 published disease-associated variants [National Heart, Lung, and Blood Institute working group et al., 2010; Cassa et al., 2012]. Full disclosure and non-disclosure policies are not appropriate for handling this multitude of genetic IF [Ravitsky and Wilfond, 2006; McGuire and Lupski, 2010]. Full disclosure is simply not feasible, being too laborious and time consuming for current clinical practice, and non-disclosure is not ethically defensible because IF may have serious medical implications [Ravitsky and Wilfond, 2006; Knoppers et al., 2006; McGuire and Lupski, 2010; Sharp, 2011; Thorogood et al., 2012]. Therefore, an intermediate Additional supporting information may be found in the online version of this article. Conflict of interest: none. *Correspondence to: Zoe Lohn, Medical Genetics Research Unit, Children’s and Women’s Health Centre of British Columbia, 4500 Oak Street, Vancouver, BC, Canada V6H 3N1. E-mail: zoelohn@gmail.com Article first published online in Wiley Online Library (wileyonlinelibrary.com): 7 February 2013 DOI 10.1002/ajmg.a.35794 How to Cite this Article: Lohn Z, Adam S, Birch PH, Townsend A, Friedman JM. 2013. Genetics professionals’ perspectives on reporting incidental findings from clinical genome-wide sequencing Am J Med Genet Part A 161A:542–549. Ó 2013 Wiley Periodicals, Inc. 542