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

Abstract

Purpose

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.

Methods

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).

Results

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.

Conclusion

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.

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Acknowledgements

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.

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Disclosure

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.

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

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Keywords

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