Psychological outcomes related to exome and genome sequencing result disclosure: a meta-analysis of seven Clinical Sequencing Exploratory Research (CSER) Consortium studies



As exome and genome sequencing (ES/GS) enters the clinic, there is an urgent need to understand the psychological effects of test result disclosure. Through a Clinical Sequencing Exploratory Research (CSER), phase 1 (CSER1) Consortium collaboration, we evaluated participants’ psychological outcomes across multiple clinical settings.


We conducted a random effects meta-analysis of state anxiety (Hospital Anxiety and Depression Scale [HADS]/Generalized Anxiety Disorder 7-item), depressive symptoms (HADS/Personal Health Questionnaire 9-item), and multidimensional impact (i.e., test-related distress, uncertainty and positive impact: modified Multidimensional Impact of Cancer Risk Assessment/Feelings About Genomic Testing Results scale).


Anxiety and depression did not increase significantly following test result disclosure. Meta-analyses examining mean differences from pre- to postdisclosure revealed an overall trend for a decrease in participants’ anxiety. We observed low levels of test-related distress and perceptions of uncertainty in some populations (e.g., pediatric patients) and a wide range of positive responses.


Our findings across multiple clinical settings suggest no clinically significant psychological harms from the return of ES/GS results. Some populations may experience low levels of test-related distress or greater positive psychological effects. Future research should further investigate the reasons for test-related psychological response variation.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2


  1. 1.

    National Academies of Sciences, Engineering, and Medicine. Returning individual research results to participants: guidance for a new research paradigm. Washington, DC: The National Academies Press; 2018.

  2. 2.

    Wynn J, Martinez J, Duong J, et al. Research participants’ preferences for hypothetical secondary results from genomic research. J Genet Couns. 2017;26:841–851.

  3. 3.

    Appelbaum PS, Fyer A, Klitzman RL, et al. Researchers’ views on informed consent for return of secondary results in genomic research. Genet Med. 2015;17:644–650.

  4. 4.

    Townsend A, Adam S, Birch PH, Lohn Z, Rousseau F, Friedman JM. “I want to know what’s in Pandora’s Box”: comparing stakeholder perspectives on incidental findings in clinical whole genomic sequencing. Am J Med Genet A. 2012;158a:2519–2525.

  5. 5.

    Bollinger JM, Scott J, Dvoskin R, Kaufman D. Public preferences regarding the return of individual genetic research results: findings from a qualitative focus group study. Genet Med. 2012;14:451–457.

  6. 6.

    Rini C, Khan CM, Moore E, et al. The who, what, and why of research participants’ intentions to request a broad range of secondary findings in a diagnostic genomic sequencing study. Genet Med. 2018;20:760–769.

  7. 7.

    Green RC, Roberts JS, Cupples LA, et al. Disclosure of APOE genotype for risk of Alzheimer’s disease. N Engl J Med. 2009;361:245–254.

  8. 8.

    Heshka JT, Palleschi C, Howley H, Wilson B, Wells PS. A systematic review of perceived risks, psychological and behavioral impacts of genetic testing. Genet Med. 2008;10:19–32.

  9. 9.

    Peterson EB, Chou WS, Gaysynsky A, et al. Communication of cancer-related genetic and genomic information: a landscape analysis of reviews. Transl Behav Med. 2018;8:59–70.

  10. 10.

    Crozier S, Robertson N, Dale M. The psychological impact of predictive genetic testing for Huntington’s disease: a systematic review of the literature. J Genet Couns. 2015;24:29–39.

  11. 11.

    Wakefield CE, Hanlon LV, Tucker KM, et al. The psychological impact of genetic information on children: a systematic review. Genet Med. 2016;18:755–762.

  12. 12.

    Wynn J, Ottman R, Duong J, et al. Diagnostic exome sequencing in children: a survey of parental understanding, experience and psychological impact. Clin Genet. 2018;93:1039–1048.

  13. 13.

    Sanderson SC, Linderman MD, Suckiel SA, et al. Psychological and behavioural impact of returning personal results from whole-genome sequencing: the HealthSeq project. Eur J Hum Genet. 2017;25:280–292.

  14. 14.

    Green RC, Goddard KA, Jarvik GP, et al. Clinical Sequencing Exploratory Research Consortium: accelerating evidence-based practice of genomic medicine. Am J Hum Genet. 2016;98:1051–1066.

  15. 15.

    Gray SW, Martins Y, Feuerman LZ, et al. Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group. Genet Med. 2014;16:727–735.

  16. 16.

    Athens BA, Caldwell SL, Umstead KL, Connors PD, Brenna E, Biesecker BB. A systematic review of randomized controlled trials to assess outcomes of genetic counseling. J Genet Couns. 2017;26:902–933.

  17. 17.

    Berg JS, Amendola LM, Eng C, et al. Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the Clinical Sequencing Exploratory Research Consortium. Genet Med. 2013;15:860–867.

  18. 18.

    Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–370.

  19. 19.

    Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606–613.

  20. 20.

    Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092–1097.

  21. 21.

    Cella D, Hughes C, Peterman A, et al. A brief assessment of concerns associated with genetic testing for cancer: the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire. Health Psychol. 2002;21:564–572.

  22. 22.

    Li M, Bennette CS, Amendola LM, et al. The Feelings About genomiC Testing Results (FACToR) Questionnaire: Development and Preliminary Validation. J Genet Couns. 2019;28:477–490.

  23. 23.

    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188.

  24. 24.

    Stata Statistical Software [computer program]. Version 13.1. College Station, TX: StataCorp LP; 2013.

  25. 25.

    Broady KM, Ormond KE, Topol EJ, Schork NJ, Bloss CS. Predictors of adverse psychological experiences surrounding genome-wide profiling for disease risk. J Community Genet. 2018;9:217–225.

  26. 26.

    Vassy JL, Christensen KD, Schonman EF, et al. The impact of whole-genome sequencing on the primary care and outcomes of healthy adult patients: a pilot randomized trial. Ann Intern Med. 2017;167:159–169.

  27. 27.

    Lumish HS, Steinfeld H, Koval C, et al. Impact of panel gene testing for hereditary breast and ovarian cancer on patients. J Genet Couns. 2017;26:1116–1129.

  28. 28.

    Low CA, Bower JE, Kwan L, Seldon J. Benefit finding in response to BRCA1/2 testing. Ann Behav Med. 2008;35:61–69.

  29. 29.

    Krabbenborg L, Vissers LE, Schieving J, et al. Understanding the psychosocial effects of WES test results on parents of children with rare diseases. J Genet Couns. 2016;25:1207–1214.

  30. 30.

    Rosell AM, Pena LD, Schoch K, et al. Not the end of the odyssey: parental perceptions of whole exome sequencing (WES) in pediatric undiagnosed disorders. J Genet Couns. 2016;25:1019–1031.

  31. 31.

    Malek J, Slashinski MJ, Robinson JO, et al. Parental perspectives on whole-exome sequencing in pediatric cancer: a typology of perceived utility. JCO Precision Oncology. 2017.

  32. 32.

    Sapp JC, Dong D, Stark C, et al. Parental attitudes, values, and beliefs toward the return of results from exome sequencing in children. Clin Genet. 2014;85:120–126.

  33. 33.

    Biesecker BB, Erby LH, Woolford S, et al. Development and validation of the Psychological Adaptation Scale (PAS): use in six studies of adaptation to a health condition or risk. Patient Educ Couns. 2013;93:248–254.

  34. 34.

    Christensen KD, Green RC How could disclosing incidental information from whole-genome sequencing affect patient behavior? Pers Med. 2013;10.

  35. 35.

    McBride CM, Koehly LM, Sanderson SC, Kaphingst KA. The behavioral response to personalized genetic information: will genetic risk profiles motivate individuals and families to choose more healthful behaviors? Annu Rev Public Health. 2010;31:89–103.

  36. 36.

    Amendola LM, Berg JS, Horowitz CR, et al. The Clinical Sequencing Evidence-Generating Research Consortium: integrating genomic sequencing in diverse and medically underserved pPopulations. Am J Hum Genet. 2018;103:319–327.

  37. 37.

    Crawford DC, Crosslin DR, Tromp G, et al. eMERGEing progress in genomics—the first seven years. Front Genet. 2014;5:184.

  38. 38.

    All of Us. 2018. Accessed 14 March 2018.

  39. 39.

    Berg JS, Agrawal PB, Bailey DB Jr, et al. Newborn sequencing in genomic medicine and public health. Pediatrics. 2017;139.

Download references


The CSER Consortium was funded by the National Human Genome Research Institute (NHGRI) and the National Cancer Institute (NCI), supporting the following sites: CSER Coordinating Center U01HG007307, NEXT Medicine U01HG006507, MedSeq U01HG006500, PediSeq U01HG006546, DFCI U01HG006492, NCGENES U01HG006487. ClinSeq® is supported by ZIAHG200359 09 and ZIAHG200387 04 from the Intramural Research Program of the NHGRI. The Columbia ROR project was supported by R21 HG006596 (Dr. Appelbaum, principal investigator [PI]), R01 HG006600 (Drs. Chung and Phelan, PIs), P50 HG007257 (Dr. Appelbaum, PI), UL1 TR000040, and UL1 RR024156.

Author information

Correspondence to Stacy W. Gray MD, AM.

Ethics declarations


K.D.C. has received travel funds from Illumina, Inc. S.W.G. serves as a consultant to GRAIL. R.C.G. advises AIA, Applied Therapeutics, Helix, Ohana, OptraHealth, Prudential, Verily, and Veritas, and is cofounder of Genome Medical, Inc. Funding for B. Biesecker’s contributions came from the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. L.G.B. is a member of Illumina Medical Ethics Advisory Board, receives royalties from Genentech, receives in-kind research support from ArQule, Inc, honoraria from Cold Spring Harbor Press, and is supported by the Intramural Research Program of NHGRI, grant HG200387 04. The other authors declare no conflicts of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Co-first authors: Jill O. Robinson and Julia Wynn

Supplementary information

Supplementary Information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark


  • exome sequencing
  • genome sequencing
  • return of results
  • patient-reported outcomes
  • psychological effect