Clinical Genome Sequencing: Psychological Considerations

Cover
Clinical Genome Sequencing: Psychological Considerations
Copyright
Dedication
List of Contributors
1 Genetic Testing Expanded
	Introduction
	Genomics and Single-Gene Testing
	The Era of Single Testing
	Consent to Genome Sequencing
	Direct-to-Consumer Testing
	Genomics and Personalized Medicine
	Genetic Counseling for Single-Gene Testing: A Paradigm for Genomic Testing?
	Genome Sequencing in Pediatrics
	Genome Sequencing and Reproductive Issues
	Psychological Studies in Genomics
	Concluding Remarks
	References
2 Genome Sequencing and Individual Responses to Results
	Use of Sequencing and How It Extends Beyond Genetic Testing
	Clinical Utility of Results From Sequencing
		Diagnosis of rare diseases and disease susceptibility
		Tumor identification and targeted treatment
		Carrier testing and screening
		Secondary findings
		Pharmacogenetic testing
		Psychological responses to results
		Reporting to relatives and cascade testing
	Personal Utility
		The future use of genome sequencing for health
	References
	Further Reading
3 Consenting Patients to Genome Sequencing
	Informed Consent: An Introduction
	Challenges of Informed Consent in Clinical Genomics
	What Should Informed Consent for Genomic Sequencing Ideally Look Like? Insights From Normative Documents
		Legislation addressing informed consent
			International guidance
			European Union regulations
			National legislations in European countries
		Professional guidelines and recommendations
			Need to establish a responsible consent process
			Overlapping areas: genetic counseling and informed consent
			Need for explicit informed consent for genomic sequencing and research
			Responsibility of different professionals in the process of informed consent: much seems to rest on the genetic clinician y...
			What needs to be included in the informed consent process?
	Empirical Studies on the Process of Informed Consent for Genomic Sequencing
		Informed consent documents: what can we learn about practice?
			Variety in elements addressed in informed consent forms
			Secondary and unsolicited findings in informed consent forms
			Readability of informed consent forms
			Informed consent for WES/WGS offered directly-to-consumers
		Stakeholders’ views and experiences of the informed consent process
			Healthcare professional views and experience
			Patients’ perspective
	Specific Contexts Necessitating Additional Reflection and Study Regarding Informed Consent
		The case of minors
		Genomic sequencing within the context of gene editing; Russian doll model of complications?
	Conclusion
	Acknowledgments
	References
	Further Reading
4 Judgment and Decision Making in Genome Sequencing
	Introduction
	Lessons From Research on Judgment and Decision-Making
		Cognitive biases
			Use of heuristics
			Trouble with numbers
			Sensitivity to context
			Recommended approaches
		Emotional influences
		Motivational factors
			Conserving cognitive resources
			Maintaining positive self-views and affirming one’s values
			Perceiving control over personally relevant outcomes
			Regarding oneself (and being regarded by others) as a rational actor
			Engaging in normative behavior
			Avoiding loss, uncertainty, and ambiguity
			Summary
	Conclusion
	References
5 Uncertainties in Genome Sequencing
	History of Uncertainty in Genetics
	Dimensions for Uncertainties in Genome Sequencing
	Personal Uncertainties in Genome Sequencing
	The Case of Variants of Uncertain Significance
	The Potential Health Threat of Uncertainties
	Individual Differences in Tolerance of Uncertainties
	Interpretation of Uncertain Genomic Information
	Healthcare Consequences of Uncertainties
	Establishing Expectations for Uncertainties
	Concluding Remarks
	References
	Further Reading
6 Direct-to-Consumer Genetic Testing
	The Online Offer of Tests
	Critical Appraisal of Scientific Studies on DTC Genetic Testing
	Polygenic Risk Scores
	How Accurate Are Polygenic Risk Scores?
	Intentions, Understanding, and Psychological Impact
		Intentions
		Understanding
		Psychological wellbeing
	Utility of Testing
	What Are the Concerns
	References
7 Assessing the Psychological Impact of Next-Generation Sequencing Information in the Clinic: An Attempt to Map Terra Incog...
	Introduction
	Background
		Definition of terms
	Indications for Next-Generation Sequencing
		Diagnostic testing
		Pharmacogenomic testing
		Somatic testing
		Population screening
		Incidental, secondary, or additional findings
	Psychological Impact of Different Types of Next-Generation sequencing
	Diagnostic testing
	Pharmacogenomic Testing
	Somatic Testing
	Population Screening
	Conclusion
	References
	Further Reading
8 Genetic Counseling and Genomic Sequencing
	Introduction
	What Do Patients Expect From Genomic Sequencing?
	Providing Genomic Counseling
		Balancing supportive and informational needs
		Personalizing personalized medicine
		Special considerations
	Returning Results From Genomic Sequencing
		How do families respond to results from genomic sequencing?
		How should results be discussed with patients and families?
			Information is necessary, but not sufficient
			Be flexible to permit families time to digest
			Target explanations to family literacy and interests
			Discuss implications of results for family members
			Consider which clinicians or team members should be present when results are returned
			Follow-up with families to support, clarify, and refer
		Special issues with pediatric sequencing
	Current Needs and Future Trends
	References
9 Genome Sequencing in Pediatrics: Ethical Issues
	Introduction
	Current Policy Guidelines for Genomic Testing in Minors
	Empirical Ethics Research on Genomic Testing in Minors
	Translating Empirical Results Into Normative Policies
	The Ethical Debate Reconsidered
	Conclusion
	References
10 Genome Sequencing in Prenatal Testing and Screening: Lessons Learned From Broadening the Scope of Prenatal Genetics From...
	2012—A New Era in PND: Do Pregnant Couples Want a Broader Scope of Invasive Prenatal Genetic Testing?
		Methods and procedure
			Prenatal WES will be highly accepted among high-risk pregnant couples
	Are Pregnant Couples Making Informed Decisions About the Scope of Their Prenatal Genetic Test?
		Attitude-consistent prenatal decision-making will become more prominent aspects of informed decision-making
	What Is the Impact of Receiving Highly Uncertain Prenatal Genetic Test Results?
		We expect a high tolerance for uncertainty and we foresee a high need for swift and easily accessible post-test counseling ...
	2014: A New Era in PNS: The Introduction of NIPT in the Netherlands
	2017: NIPT for all Pregnant Women in the Netherlands
		Prenatal WES will be highly accepted among high-risk pregnant couples
	Measuring Informed Decision-Making in Noninvasive vs Invasive Prenatal Testing
		Informed decision-making is a prerequisite for reproductive autonomy and we need to create new measures to assess informed ...
	The Role of the Counselor in Deciding About Prenatal Genetic Testing
		Using WES in prenatal genetic testing will likely magnify the influence of the counselor
	The Psychological Impact of Deciding About the Course of a Strongly Desired Pregnancy
	Summary and Conclusion
	Acknowledgments
	References
11 Clinical Genetic Testing and Counseling in Psychiatry
	Clinical Vignette: The Impact of a Positive Family History of Mental Illness
	Introduction
	A Brief Overview of Psychiatric Genetics
		Early insights and genetic studies in psychiatry
		Chromosomal studies
		The candidate gene approach
		Mendelian genetics
		Genome-wide association studies
		Next-generation sequencing
		Polygenic inheritance
		Copy number variants
		A comparison to neurodegenerative disorders
	Current State-of-the-Art in the Clinical Psychiatric Genetics
		The impact of psychiatric disorders
		Genetic counseling for psychiatric disorders
		Empirical recurrence risks
		Syndromic forms of mental illness, and genetic testing and counseling
		Acceptance and commitment therapy
	Points of Discussion
		Family genetic studies complementary to large-scale case/control studies
		Understanding of disease etiology in neurology is derived from family studies—Why should psychiatric disorders be any diffe...
		More families need to be examined to sketch the landscape of mutations that may result in psychiatric disorders
		The genetic architecture of childhood-onset versus adult-onset psychiatric disorders
		Genetic testing in the psychiatric clinic in a subgroup of complex patients
		Clinicians working in psychiatry should be trained in human molecular genetics
		Genetics might change the classification system of psychiatric disorders based on the molecular disturbance rather than the...
	Concluding Remarks
	References
	Further Reading
12 Opportunistic Genomic Screening: Ethical Exploration*
	Introduction
	The Wider Horizon
		The rise of personalized medicine
		NGS: a catalyst for PM
	OGS: The ACMG’s and SFMPP’s Proposals
		The concept and rationale of OGS
		The ACMG’s proposal
			ACMG/OGS 1.0
			ACMG/OGS 2.0
		The SFMPP’s proposal
	Ethical Exploration
		Introduction: screening criteria
		OGS in competent adult patients
			Proportionality
				Possible benefits
				Risks
			Respect for autonomy
				The decision whether or not to have oneself tested beyond the initial indication
				“All or nothing”—that is to say: a “coercive offer” (ACMG/OGS 1.0)
				“Opt out” (ACMG/OGS 2.0)
				Deciding about the scope or content of the test
			Justice
				Need versus opportunity
				Equity versus opportunity
		OGS in children
	Conclusions
	References
13 Summary of Key Areas for Research
	The Healthcare Provider’s Perspective
	The Patient's or Consumer’s Perspective
	References
Index
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