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Journal of Genetic Counseling

, Volume 23, Issue 4, pp 463–473 | Cite as

Incidental Findings from Clinical Genome-Wide Sequencing: A Review

  • Z. LohnEmail author
  • S. Adam
  • P. H. Birch
  • J. M. Friedman
Next Generation Genetic Counseling

Abstract

There are several unresolved challenges associated with the clinical application of genome-wide sequencing technologies. One of the most discussed issues is incidental findings (IF), which are defined as discoveries made as a result of genetic testing that are unrelated to the indication for the test. The discussion surrounding IF began in the context of research, which we have used to frame consideration of IF in the clinical context. There is growing consensus that analytically valid and medically actionable IF should be offered to patients, but whether and to what extent clinicians should disclose other kinds of IF is debated. While others have systematically reviewed the literature concerning genetic IF, previous reviews focus on ethical and research-related issues and do not consider the implications for the genetic counseling profession specifically. This review discusses the practical considerations, ethical concerns and genetic counseling issues related to IF, with a particular focus on clinical genome-wide sequencing. To date, the bulk of the literature with respect to IF in the clinical context consists of commentaries, reviews and case reports. There is a need for more empirical studies to provide a foundation for institutional protocols and evidence-based clinical practice standards.

Keywords

Incidental finding Secondary finding Whole genome sequencing Whole exome sequencing Genetic counseling Clinical genetics Return of results Sequencing Genomic medicine Personalized medicine 

Notes

Acknowledgments

We would like to thank APOGEE-Net/CanGèneTest Research and Knowledge Network on Genetic Health Services and Policy. We would also like to thank Dr. Jehannine Austin for her careful reading of the manuscript. We have no conflict of interest to disclose.

References

  1. Ali-Khan, S. E., Daar, A. S., Shuman, C., Ray, P. N., & Scherer, S. W. (2009). Whole genome scanning: resolving clinical diagnosis and management amidst complex data. Pediatric Research, 66, 357–363.CrossRefGoogle Scholar
  2. Ashley, E. A., Butte, A. J., Wheeler, M. T., Chen, R., Klein, T. E., Dewey, F. E., et al. (2010). Clinical assessment incorporating a personal genome. Lancet, 375, 1525–1535.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Avard, D., Senecal, K., Madadi, P., & Sinnett, D. (2011). Pediatric research and the return of individual research results. The Journal of Law, Medicine & Ethics, 39, 593–604.CrossRefGoogle Scholar
  4. Ayuso, C., Millan, J.M., Mancheno, M., Dal-Re, R. (2013). Informed consent for whole-genome sequencing studies in the clinical setting. proposed recommendations on essential content and process. European Journal of Human Genetics [Epub ahead of print].Google Scholar
  5. Bamshad, M. J., Ng, S. B., Bigham, A. W., Tabor, H. K., Emond, M. J., Nickerson, D. A., et al. (2011). Exome sequencing as a tool for mendelian disease gene discovery. Nature Reviews Genetics, 12, 745–755.CrossRefGoogle Scholar
  6. Berg, J. S., Khoury, M. J., & Evans, J. P. (2011). Deploying whole genome sequencing in clinical practice and public health: meeting the challenge one bin at a time. Genetics in Medicine, 13, 499–504.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Berg, J. S., Adams, M., Nassar, N., Bizon, C., Lee, K., Schmitt, C. P., et al. (2012). An informatics approach to analyzing the incidentalome. Genetics in Medicine, 15, 36–44.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bevan, J. L., Senn-Reeves, J. N., Inventor, B. R., Greiner, S. M., Mayer, K. M., Rivard, M. T., et al. (2012). Critical social theory approach to disclosure of genomic incidental findings. Nursing Ethics, 19, 819–828.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bloss, C. S., Ornowski, L., Silver, E., Cargill, M., Vanier, V., Schork, N. J., et al. (2010). Consumer perceptions of direct-to-consumer personalized genomic risk assessments. Genetics in Medicine, 12, 556–566.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bollinger, J. M., Scott, J., Dvoskin, R., & Kaufman, D. (2012). Public preferences regarding the return of individual genetic research results: findings from a qualitative focus group study. Genetics in Medicine, 14, 451–457.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bookman, E. B., Langehorne, A. A., Eckfeldt, J. H., Glass, K. C., Jarvik, G. P., Klag, M., NHLBI Working Group, et al. (2006). Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. American Journal of Medical Genetics. Part A, 140, 1033–1040.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Borry, P., Stultiens, L., Nys, H., Cassiman, J. J., & Dierickx, K. (2006). Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers. Clinical Genetics, 70, 374–381.CrossRefGoogle Scholar
  13. Bradbury, A. R., Patrick-Miller, L., Pawlowski, K., Ibe, C. N., Cummings, S. A., Olopade, O. I., et al. (2008). Should genetic testing for BRCA1/2 be permitted for minors? opinions of BRCA mutation carriers and their adult offspring. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 148C, 70–77.CrossRefGoogle Scholar
  14. Bredenoord, A. L., Kroes, H. Y., Cuppen, E., Parker, M., & van Delden, J. J. (2011). Disclosure of individual genetic data to research participants: the debate reconsidered. Trends in Genetics, 27, 41–47.CrossRefGoogle Scholar
  15. Catz, D. S., Green, N. S., Tobin, J. N., Lloyd-Puryear, M. A., Kyler, P., Umemoto, A., et al. (2005). Attitudes about genetics in underserved, culturally diverse populations. Community Genetics, 8, 161–172.PubMedPubMedCentralGoogle Scholar
  16. Caulfield, T., McGuire, A. L., Cho, M., Buchanan, J. A., Burgess, M. M., Danilczyk, U., et al. (2008). Research ethics recommendations for whole-genome research: consensus statement. PLoS Biology, 6, e73.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Cho, M. K. (2008). Understanding incidental findings in the context of genetics and genomics. The Journal of Law, Medicine & Ethics, 36, 280–285.CrossRefGoogle Scholar
  18. Christenhusz, G. M., Devriendt, K., & Dierickx, K. (2013). To tell or not to tell? A systematic review of ethical reflections on incidental findings arising in genetics contexts. European Journal of Human Genetics, 21, 248–55.CrossRefGoogle Scholar
  19. Clayton, E. W. (2008). Incidental findings in genetics research using archived DNA. The Journal of Law, Medicine & Ethics, 36, 286–291.CrossRefGoogle Scholar
  20. Davis, D. S. (1997). Genetic dilemmas and the child’s right to an open future. The Hastings Center Report, 27, 7–15.CrossRefGoogle Scholar
  21. Dimmock, D. (2012). A personal perspective on returning secondary results of clinical genome sequencing. Genome Medicine, 4, 54.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Downing, N. R., Williams, J. K., Daack-Hirsch, S., Driessnack, M., & Simon, C. M. (2013). Genetics specialists’ perspectives on disclosure of genomic incidental findings in the clinical setting. Patient Education and Counseling, 90, 133–138.CrossRefGoogle Scholar
  23. Drmanac, R. (2011). The advent of personal genome sequencing. Genetics in Medicine, 13, 188–190.CrossRefGoogle Scholar
  24. Evans, J. P., & Rothschild, B. B. (2012). Return of results: not that complicated? Genetics in Medicine, 14, 358–360.CrossRefGoogle Scholar
  25. Facio, F. M., Brooks, S., Loewenstein, J., Green, S., Biesecker, L. G., & Biesecker, B. B. (2011). Motivators for participation in a whole-genome sequencing study: Implications for translational genomics research. European Journal of Human Genetics, 19, 1213–1217.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Fernandez CV, Strahlendorf C, Avard D, Knoppers BM, O’Connell C, Bouffet E et al. 2013. Attitudes of canadian researchers toward the return to participants of incidental and targeted genomic findings obtained in a pediatric research setting. Medical Genetics [Epub ahead of print].Google Scholar
  27. Foster, M. W., Mulvihill, J. J., & Sharp, R. R. (2009). Evaluating the utility of personal genomic information. Genetics in Medicine, 11, 570–574.CrossRefGoogle Scholar
  28. Goldsmith, L., Jackson, L., O’Connor, A., & Skirton, H. (2012). Direct-to-consumer genomic testing: Systematic review of the literature on user perspectives. European Journal of Human Genetics, 20, 811–816.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Gonzaga-Jauregui, C., Lupski, J. R., & Gibbs, R. A. (2012). Human genome sequencing in health and disease. Annual Review of Medicine, 63, 35–61.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Green, M. J., Peterson, S. K., Baker, M. W., Harper, G. R., Friedman, L. C., Rubinstein, W. S., et al. (2004). Effect of a computer-based decision aid on knowledge, perceptions, and intentions about genetic testing for breast cancer susceptibility: a randomized controlled trial. JAMA, 292, 442–452.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Green, M. J., Peterson, S. K., Baker, M. W., Friedman, L. C., Harper, G. R., Rubinstein, W. S., et al. (2005). Use of an educational computer program before genetic counseling for breast cancer susceptibility: Effects on duration and content of counseling sessions. Genetics in Medicine, 7, 221–229.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Green, R. C., Berg, J. S., Berry, G. T., Biesecker, L. G., Dimmock, D. P., Evans, J. P., et al. (2012). Exploring concordance and discordance for return of incidental findings from clinical sequencing. Genetics in Medicine, 14, 405–410.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Green, R.C., Berg, J.S., Grody, W.W., Kalia, S.S., Korf, B.R., et al. (2013). The American College of Medical Genetics and Genomics (ACMG) Recommendations for reporting of incidental findings in clinical exome and genome sequencing March 21 2013 (1–29). https://doi.org/www.acmg.net/docs/ACMG_Releases_HighlyAnticipated_Recommendations_on_Incidental_Findings_in_Clinical_Exome_and_Genome_Sequencing.pdf. Accessed 21 March 2013.
  34. Grosse, S. D., McBride, C. M., Evans, J. P., & Khoury, M. J. (2009). Personal utility and genomic information: look before you leap. Genetics in Medicine, 11, 575–576.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Haga, S. B., O’daniel, J. M., Tindall, G. M., Lipkus, I. R., & Agans, R. (2011). Public attitudes toward ancillary information revealed by pharmacogenetic testing under limited information conditions. Genetics in Medicine, 13, 723–728.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Halverson, C. M., & Ross, L. F. (2012). Incidental findings of therapeutic misconception in biobank-based research. Genetics in Medicine, 14, 611–615.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Harris, E. D., Ziniel, S. I., Amatruda, J. G., Clinton, C. M., Savage, S. K., Taylor, P. L., et al. (2012). The beliefs, motivations, and expectations of parents who have enrolled their children in a genetic biorepository. Genetics in Medicine, 14, 330–337.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Heald, B., Moran, R., Milas, M., Burke, C., & Eng, C. (2007). Familial adenomatous polyposis in a patient with unexplained mental retardation. Nature Clinical Practice Neurology, 3, 694–700.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Henderson, G. E. (2011). Is informed consent broken? The American Journal of the Medical Sciences, 42, 267–72.CrossRefGoogle Scholar
  40. Henneman, L., Timmermans, D. R., & van der Wal, G. (2004). Public experiences, knowledge and expectations about medical genetics and the use of genetic information. Community Genetics, 7, 33–43.Google Scholar
  41. Hens, K., Nys, H., Cassiman, J. J., & Dierickx, K. (2011). The return of individual research findings in paediatric genetic research. Journal of Medical Ethics, 37, 179–183.CrossRefGoogle Scholar
  42. Hens, K., Van El, C. E., Borry, P., Cambon-Thomsen, A., Cornel, M. C., Forzano, F., et al. (2013). Developing a policy for paediatric biobanks: principles for good practice. European Journal of Human Genetics, 21, 2–7.CrossRefGoogle Scholar
  43. Hogan, J., Turner, A., Tucker, K., & Warwick, L. (2013). Unintended diagnosis of von hippel lindau syndrome using array comparative genomic hybridization (CGH): Counseling challenges arising from unexpected information. Journal of Genetic Counseling, 22, 22–26.CrossRefGoogle Scholar
  44. Jackson, L., Goldsmith, L., O’Connor, A., & Skirton, H. (2012). Incidental findings in genetic research and clinical diagnostic tests: a systematic review. American Journal of Medical Genetics. Part A, 12, 3159–3167.CrossRefGoogle Scholar
  45. Johnston, J. J., Rubinstein, W. S., Facio, F. M., Ng, D., Singh, L. N., Teer, J. K., et al. (2012). Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. American Journal of Human Genetics, 91, 97–108.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Kaye, J., Boddington, P., de Vries, J., Hawkins, N., & Melham, K. (2010). Ethical implications of the use of whole genome methods in medical research. European Journal of Human Genetics, 18, 398–403.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Knoppers, B. M., Joly, Y., Simard, J., & Durocher, F. (2006). The emergence of an ethical duty to disclose genetic research results: international perspectives. European Journal of Human Genetics, 14, 1170–1178.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Kohane, I. S., & Taylor, P. L. (2010). Multidimensional results reporting to participants in genomic studies: getting it right. Science Translational Medicine, 2, 37–19.CrossRefGoogle Scholar
  49. Kohane, I. S., Masys, D. R., & Altman, R. B. (2006). The incidentalome: a threat to genomic medicine. JAMA, 296, 212–215.CrossRefGoogle Scholar
  50. Kohane, I. S., Mandl, K. D., Taylor, P. L., Holm, I. A., Nigrin, D. J., & Kunkel, L. M. (2007). Medicine. reestablishing the researcher-patient compact. Science, 316, 836–837.CrossRefGoogle Scholar
  51. Kohane, I. S., Hsing, M., & Kong, S. W. (2012). Taxonomizing, sizing, and overcoming the incidentalome. Genetics in Medicine, 14, 399–404.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Lanie, A. D., Jayaratne, T. E., Sheldon, J. P., Kardia, S. L., Anderson, E. S., Feldbaum, M., et al. (2004). Exploring the public understanding of basic genetic concepts. Journal of Genetic Counseling, 13, 305–320.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Lavieri, R. R., & Garner, S. A. (2006). Ethical considerations in the communication of unexpected information with clinical implications. The American Journal of Bioethics, 6, 46–48.CrossRefGoogle Scholar
  54. Lawrenz, F., & Sobotka, S. (2008). Empirical analysis of current approaches to incidental findings. The Journal of Law, Medicine & Ethics, 36, 249–255.CrossRefGoogle Scholar
  55. Lemke A, Bick D, Dimmock D, Simpson P, Veith R. 2012. Perspectives of clinical genetics professionals toward genome sequencing and incidental findings: a survey study. Clinical Genetics [Epub ahead of print].Google Scholar
  56. Lewis, A., & James, P. (2012). An incidental finding of a large genomic deletion of BRCA1 on a molecular karyotype for a 5 year old child. Hereditary Cancer in Clinical Practice, 10(Suppl 2), A73.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Lohn, Z., Adam, S., Birch, P. H., Townsend, A., & Friedman, J. M. (2013). Genetics professionals’ perspectives on reporting incidental findings from clinical genome-wide sequencing. American Journal of Medical Genetics, 161, 542–549.CrossRefGoogle Scholar
  58. Lumbreras, B., Donat, L., & Hernandez-Aguado, I. (2010). Incidental findings in imaging diagnostic tests: a systematic review. British Journal of Radiology, 83, 276–289.CrossRefGoogle Scholar
  59. Lyon, G. J., Jiang, T., Van Wijk, R., Wang, W., Bodily, P. M., Xing, J., et al. (2011). Exome sequencing and unrelated findings in the context of complex disease research: ethical and clinical implications. Discovery Medicine, 12, 41–55.PubMedPubMedCentralGoogle Scholar
  60. MacArthur, D. G., Balasubramanian, S., Frankish, A., Huang, N., Morris, J., Walter, K., et al. (2012). A systematic survey of loss-of-function variants in human protein-coding genes. Science, 335, 823–828.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Maheu, C., & Thorne, S. (2008). Receiving inconclusive genetic test results: an interpretive description of the BRCA1/2 experience. Research in Nursing & Health, 31, 553–562.CrossRefGoogle Scholar
  62. Matutina, R. E. (2010). The concept analysis of therapeutic misconception. Nurse Researcher, 17, 83–90.CrossRefGoogle Scholar
  63. Mayer, A. N., Dimmock, D. P., Arca, M. J., Bick, D. P., Verbsky, J. W., Worthey, E. A., et al. (2011). A timely arrival for genomic medicine. Genetics in Medicine, 13, 195–196.CrossRefGoogle Scholar
  64. McGuire, A. L., & Lupski, J. R. (2010). Personal genome research: what should the participant be told? Trends in Genetics, 26, 199–201.CrossRefGoogle Scholar
  65. McGuire, A. L., Caulfield, T., & Cho, M. K. (2008). Research ethics and the challenge of whole-genome sequencing. Nature Reviews Genetics, 9, 152–156.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Meacham, M. C., Starks, H., Burke, W., & Edwards, K. (2010). Researcher perspectives on disclosure of incidental findings in genetic research. Journal of Empirical Research on Human Research Ethics, 5, 31–41.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Mesters, I., Ausems, A., & De Vries, H. (2005). General public’s knowledge, interest and information needs related to genetic cancer: an exploratory study. European Journal of Cancer Prevention, 14, 69–75.CrossRefGoogle Scholar
  68. Meulenkamp, T. M., Gevers, S. K., Bovenberg, J. A., Koppelman, G. H., van Hylckama, V. A., & Smets, E. M. (2010). Communication of biobanks’ research results: what do (potential) participants want? American Journal of Medical Genetics. Part A, 152A, 2482–2492.CrossRefGoogle Scholar
  69. Michie, S., Dormandy, E., & Marteau, T. M. (2003). Informed choice: understanding knowledge in the context of screening uptake. Patient Education and Counseling, 50, 247–253.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Miller, F. A., Hayeems, R. Z., Bombard, Y., Little, J., Carroll, J. C., Wilson, B., et al. (2009). Clinical obligations and public health programmes: healthcare provider reasoning about managing the incidental results of newborn screening. Journal of Medical Ethics, 35, 626–634.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Miller, F. A., Hayeems, R. Z., Li, L., & Bytautas, J. P. (2012). One thing leads to another: the cascade of obligations when researchers report genetic research results to study participants. European Journal of Human Genetics, 20, 837–843.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Molster, C., Charles, T., Samanek, A., & O’Leary, P. (2009). Australian study on public knowledge of human genetics and health. Public Health Genomics, 12, 84–91.CrossRefGoogle Scholar
  73. Murphy, J., Scott, J., Kaufman, D., Geller, G., LeRoy, L., & Hudson, K. (2008). Public expectations for return of results from large-cohort genetic research. The American Journal of Bioethics, 8, 36–43.CrossRefGoogle Scholar
  74. National Heart, Lung, and Blood Institute working group, Fabsitz, R. R., McGuire, A., Sharp, R. R., Puggal, M., Beskow, L. M., Biesecker, L. G., et al. (2010). Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a national heart, lung, and blood institute working group. Circulation. Cardiovascular Genetics, 3, 574–580.CrossRefGoogle Scholar
  75. Need, A. C., Shashi, V., Hitomi, Y., Schoch, K., Shianna, K. V., McDonald, M. T., et al. (2012). Clinical application of exome sequencing in undiagnosed genetic conditions. Journal of Medical Genetics, 49, 353–361.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Netzer, C., Klein, C., Kohlhase, J., & Kubisch, C. (2009). New challenges for informed consent through whole genome array testing. Journal of Medical Genetics, 46, 495–496.PubMedPubMedCentralCrossRefGoogle Scholar
  77. O’Daniel, J., & Haga, S. B. (2011). Public perspectives on returning genetics and genomics research results. Public Health Genomics, 14, 346–55.PubMedPubMedCentralCrossRefGoogle Scholar
  78. O’Daniel, J. M., & Lee, K. (2012). Whole-genome and whole-exome sequencing in hereditary cancer: impact on genetic testing and counseling. Cancer Journal, 18, 287–292.CrossRefGoogle Scholar
  79. O’Neill, S. C., DeMarco, T., Peshkin, B. N., Rogers, S., Rispoli, J., Brown, K., et al. (2006). Tolerance for uncertainty and perceived risk among women receiving uninformative BRCA1/2 test results. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 142, 251–259.CrossRefGoogle Scholar
  80. Parker, L. S. (2008). The future of incidental findings: should they be viewed as benefits? The Journal of Law, Medicine & Ethics, 36, 341–351.CrossRefGoogle Scholar
  81. Ravitsky, V., & Wilfond, B. S. (2006). Disclosing individual genetic results to research participants. The American Journal of Bioethics, 6, 8–17.CrossRefGoogle Scholar
  82. Rotimi, C. N., & Marshall, P. A. (2010). Tailoring the process of informed consent in genetic and genomic research. Genome Medicine, 2, 20.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Schwarzbraun, T., Obenauf, A. C., Langmann, A., Gruber-Sedlmayr, U., Wagner, K., Speicher, M. R., et al. (2009). Predictive diagnosis of the cancer prone li-fraumeni syndrome by accident: new challenges through whole genome array testing. Journal of Medical Genetics, 46, 341–344.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Semaka, A., Balneaves, L. G., & Hayden, M. R. (2013). “Grasping the grey”: patient understanding and interpretation of an intermediate allele predictive test result for huntington disease. Journal of Genetic Counseling, 22, 200–17.CrossRefGoogle Scholar
  85. Sharp, R. R. (2011). Downsizing genomic medicine: approaching the ethical complexity of whole-genome sequencing by starting small. Genetics in Medicine, 13, 191–194.CrossRefGoogle Scholar
  86. Sharp, H. M., & Orr, R. D. (2004). When “minimal risk” research yields clinically-significant data, maybe the risks aren’t so minimal. The American Journal of Bioethics, 4, W32–6.CrossRefGoogle Scholar
  87. Simon, C. M., Williams, J. K., Shinkunas, L., Brandt, D., Daack-Hirsch, S., & Driessnack, M. (2011). Informed consent and genomic incidental findings: IRB chair perspectives. Journal of Empirical Research on Human Research Ethics, 6, 53–67.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Stack, C. B., Gharani, N., Gordon, E. S., Schmidlen, T., Christman, M. F., & Keller, M. A. (2011). Genetic risk estimation in the coriell personalized medicine collaborative. Genetics in Medicine, 13, 131–139.CrossRefGoogle Scholar
  89. Tabor, H. K., & Cho, M. K. (2007). Ethical implications of array comparative genomic hybridization in complex phenotypes: points to consider in research. Genetics in Medicine, 9, 626–631.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Tabor, H. K., Stock, J., Brazg, T., McMillin, M. J., Dent, K. M., Yu, J. H., et al. (2012). Informed consent for whole genome sequencing: a qualitative analysis of participant expectations and perceptions of risks, benefits, and harms. American Journal of Medical Genetics. Part A, 158A, 1310–1319.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Tarini, B. A., Singer, D., Clark, S. J., & Davis, M. M. (2009). Parents’ interest in predictive genetic testing for their children when a disease has no treatment. Pediatrics, 124, 432–8.CrossRefGoogle Scholar
  92. Tennessen, J. A., Bigham, A. W., O’Connor, T. D., Fu, W., Kenny, E. E., Gravel, S., et al. (2012). Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science, 337, 64–9.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Tercyak, K. P., Hensley Alford, S., Emmons, K. M., Lipkus, I. M., Wilfond, B. S., & McBride, C. M. (2011). Parents’ attitudes toward pediatric genetic testing for common disease risk. Pediatrics, 127, 1288–95.CrossRefGoogle Scholar
  94. Thorogood, A., Knoppers, B., Dondorp, W., & de Wert, G. (2012). Whole-genome sequencing and the physician. Clinical Genetics, 81, 511–513.CrossRefGoogle Scholar
  95. Townsend, A., Adam, S., Birch, P. H., Lohn, Z., Rousseau, F., & Friedman, J. M. (2012). “I want to know what’s in pandora’s box”: comparing stakeholder perspectives on incidental findings in clinical whole genomic sequencing. American Journal of Medical Genetics. Part A, 158A, 2519–2525.CrossRefGoogle Scholar
  96. Van Ness, B. (2008). Genomic research and incidental findings. The Journal of Law, Medicine & Ethics, 36, 292–297.CrossRefGoogle Scholar
  97. Wilfond, B. S., & Carpenter, K. J. (2008). Incidental findings in pediatric research. The Journal of Law, Medicine & Ethics, 36, 332–40.CrossRefGoogle Scholar
  98. Wolf, S. M. (2008). Introduction: the challenge of incidental findings. The Journal of Law, Medicine & Ethics, 36, 216–218.CrossRefGoogle Scholar
  99. Wolf, S. M., Lawrenz, F. P., Nelson, C. A., Kahn, J. P., Cho, M. K., Clayton, E. W., et al. (2008). Managing incidental findings in human subjects research: analysis and recommendations. The Journal of Law, Medicine & Ethics, 36, 219–48.CrossRefGoogle Scholar
  100. Wolf, S. M., Crock, B. N., Van Ness, B., Lawrenz, F., Kahn, J. P., Beskow, L. M., et al. (2012). Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genetics in Medicine, 14, 361–384.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2013

Authors and Affiliations

  • Z. Lohn
    • 1
    • 2
    Email author
  • S. Adam
    • 1
  • P. H. Birch
    • 1
  • J. M. Friedman
    • 1
  1. 1.Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada
  2. 2.Children’s and Women’s Health Centre of British ColumbiaVancouverCanada

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