Applied Genomics and Public Health

Cover
Applied Genomics and Public Health
Copyright
Contents
List of Contributors
Preface
1 Applied Genomics and Public Health
	1.1 Introduction
	1.2 Genomics in Health Care
	1.3 Personalized Medicine and Public Health
	1.4 Conclusion
	Acknowledgments
	References
Part I: Genomics in Healthcare
2 From Genetic Epidemiology to Exposome and Systems Epidemiology
	2.1 Genetic Variation
	2.2 What Is Genetic Epidemiology?
	2.3 Approaches Toward Identifying Genetic Variants
	2.4 Implying Genetic Loci in Disease Etiology in the Context of Family Studies—Segregation and Linkage Analysis
	2.5 Implying Genetic Loci in Disease Etiology in the Context of Genetic Association Studies
	2.6 Genome-Wide Association Studies: Principles, Opportunities, and Limitations
	2.7 Quality Control in Genome-Wide Association Studies
	2.8 Association Testing, Significance Levels, and Visualizing Associations in Genome-Wide Association Studies
	2.9 Meta-Analysis, Replication, Validation, and the Value of Imputation in Genome-Wide Association Studies
	2.10 Interpretation and Follow-Up of Genome-Wide Association Studies Findings—Challenges and Limitations
	2.11 Genetic Epidemiology—Where Do We Stand—Where Do We Go
	2.12 Heritability Gap of Genome-Wide Association Studies for Complex Diseases
	2.13 Beyond a Single Locus—Epistasis and Polygenic Risk Scores
	2.14 Clinical and Public Health Utility of Genetic Epidemiology
		2.14.1 Clinical Utility
		2.14.2 Public Health Utility
	2.15 Outlook: Exposome—Systems Epidemiology—Citizen Cohorts and Biobanks
	References
3 Rare Diseases: Genomics and Public Health
	3.1 Rare Diseases Are a Relevant Public Health Problem Worldwide
	3.2 Diagnostic Strategies
	3.3 Therapeutic Developments
	3.4 National Public Policies and Programs
	3.5 International Collaborative Initiatives
	3.6 The Role of Patient Organizations
	3.7 Data Sharing
	3.8 Rare Disease in Developing Countries
	3.9 Concluding Remarks
	Funding
	References
4 Applied Genomics and Public Health Cancer Genomics
	4.1 Introduction
	4.2 Public Health and the Global Burden of Cancer
	4.3 Cancer as a Genetic and Epigenetic Disease
	4.4 Next-Generation Sequencing Technologies
	4.5 Future Directions of Next-Generation Sequencing
	4.6 Genomic Findings in Hematologic Malignancies and Public Health
	4.7 Application of Genomics to Cancer in the Context of Public Health
		4.7.1 Germ-Line Genomics
	4.8 Special Approaches
	4.9 Conclusion
	References
	Web References
5 Genomic Basis of Psychiatric Illnesses and Response to Psychiatric Drug Treatment Modalities
	5.1 Introduction
	5.2 Genetics of Schizophrenia
	5.3 Genetics of Bipolar Disorder
	5.4 Genetics of Major Depression
	5.5 Genetics of Anxiety Disorders
	5.6 Genetics of Posttraumatic Stress Disorder
	5.7 Genetics of Substance Use Disorders
	5.8 Genetics of Eating Disorders
	5.9 Genetics of Autism Spectrum Disorder
	5.10 Genetics of Attention Deficit Hyperactivity Disorder
	5.11 Pharmacogenomics of Psychiatric Treatment Modalities
		5.11.1 Pharmacogenomics of Antipsychotic Drugs
		5.11.2 Pharmacogenomics of Antidepressant Drugs and Mood Stabilizers
	5.12 Clinical Implementation of Pharmacogenomics in Psychiatry
	5.13 Educational, Ethical, and Legal Issues
	5.14 Conclusion and Future Perspectives
	References
6 Pharmacogenomics in Clinical Care: Implications for Public Health
	6.1 Introduction
	6.2 Applications of Pharmacogenomics in Clinical Care
		6.2.1 Pharmacogenomics for Cancer Therapeutics
			6.2.1.1 Tamoxifen
			6.2.1.2 Irinotecan
			6.2.1.3 5-Fluorouracil
		6.2.2 Pharmacogenomics for Drug Treatment of Cardiovascular Diseases
			6.2.2.1 Clopidogrel
			6.2.2.2 Coumarinic oral anticoagulants
			6.2.2.3 Statins
		6.2.3 Pharmacogenomics for Psychiatric Diseases
			6.2.3.1 Lithium
			6.2.3.2 Antipsychotics
		6.2.4 Pharmacogenomics and Transplantations
	6.3 Large-Scale Programs on the Clinical Application of Pharmacogenomics
	6.4 Public Health Pharmacogenomics
	6.5 Conclusions and Future Perspectives
	Acknowledgments
	References
7 Microbial Genomics in Public Health: A Translational Risk-Response Aspect
	Abbreviations
	7.1 Introduction
	7.2 New Rules for an Old Game
		7.2.1 Countering Intelligence Obsolescence: The Temporal Window of Opportunity in Infectious Disease Outbreaks
	7.3 Requirements
	7.4 Current and Projected Outbreak Resolution Approaches
		7.4.1 Mass Spectrometry
		7.4.2 Immunoassays
		7.4.3 Genomics
		7.4.4 Arrays: The Generation - X of Microbial Genomics
	7.5 Metagenomics: The Future Is Here and Now
		7.5.1 Next-Generation Sequencing: A Robust and Flexible Tool
	7.6 Culturomics: Too Little Too Late but Occasionally Indispensable
	7.7 Expanding the Horizon
	Acknowledgments
	References
8 Genome Informatics Pipelines and Genome Browsers
	Abbreviations
	8.1 Introduction
	8.2 Big Data in Genomics
		8.2.1 Next-Generation Sequencing
		8.2.2 Data Sources
		8.2.3 Data Formats
		8.2.4 Next-Generation Sequencing Platforms
			8.2.4.1 Roche 454 pyrosequencing
			8.2.4.2 Illumina (Solexa) sequencing
			8.2.4.3 Sequencing by Oligonucleotide Ligation and Detection
			8.2.4.4 Ion Torrent sequencing
			8.2.4.5 Nanopore single-molecule sequencing
			8.2.4.6 Pacific Biosciences single-molecule real-time sequencing
	8.3 Bioinformatics Methods for Analyzing Genomic Data
		8.3.1 Next-Generation Sequencing Pipelines
			8.3.1.1 Read alignment
			8.3.1.2 Variant calling
			8.3.1.3 Downstream analysis
	8.4 Genome Browsers
		8.4.1 Web-Based Genome Browsers
		8.4.2 Genome Browser Frameworks
		8.4.3 Functionalities and Features
			8.4.3.1 Visualization
			8.4.3.2 Data retrieval and analysis
			8.4.3.3 Customization
	8.5 Conclusion
	References
9 Translational Tools and Databases in Genomic Medicine
	Abbreviations
	9.1 Introduction
	9.2 Translational Tools in Genomic Medicine
		9.2.1 Pharmacogenomics and Genome Informatics
		9.2.2 The Concept of Integrated Pharmacogenomics Assistant Services
		9.2.3 Development of an Electronic Pharmacogenomics Assistant
		9.2.4 Personalized Pharmacogenomics Profiling Using Whole Genome Sequencing
	9.3 Human Genomic Databases
		9.3.1 Database Management
		9.3.2 Genomic Database Types
			9.3.2.1 General (or central) variation databases
			9.3.2.2 Locus-specific databases
			9.3.2.3 National/ethnic genomic databases
			9.3.2.4 Other genomic database types
	9.4 Discussion
	Acknowledgment
	References
10 Genetic Testing
	10.1 Introduction
	10.2 The Historical Context of Human Genome Mapping—The Human Genome Project
	10.3 Genetic Testing
	10.4 Genetic Testing in Clinical Diagnosis
		10.4.1 Genetic Testing Services
		10.4.2 Cost and Ethical Issues of Genetic Testing
	10.5 Classification of Genetic Testing methods
		10.5.1 Diagnostic Testing
		10.5.2 Predictive Testing
		10.5.3 Carrier Testing
		10.5.4 Prenatal Testing
		10.5.5 Preimplantation Testing
		10.5.6 Pharmacogenomic Testing
		10.5.7 Newborn Screening
	10.6 Types of Diagnostic Genetic Testing
		10.6.1 Cytogenetics
			10.6.1.1 Karyotyping
			10.6.1.2 Fluorescence in situ hybridization
			10.6.1.3 Comparative genomic hybridization (CGH)
		10.6.2 Deoxyribonucleic Acid Sequencing
			10.6.2.1 Next-generation sequencing
			10.6.2.2 Single-gene panel testing
			10.6.2.3 Multigene panel testing
			10.6.2.4 Whole-genome and whole-exome sequencing in diagnostic testing
		10.6.3 Microarrays
	10.7 Allowance and Costs of Genetic Tests
	10.8 Discussion
	Acknowledgments
	References
	Further Reading
		Other Resources
Part II: Personalised Medicine and Public Health
11 Assessing the Stakeholder Landscape and Stance Point on Genomic and Personalized Medicine
	11.1 Introduction
	11.2 Identifying Stakeholders in Genomic and Personalized Medicine
	11.3 Methodology of Analyzing the Stakeholders’ Views and Opinions
	11.4 An Example of Stakeholder Analysis in Genomic and Personalized Medicine: Preliminary Assessment of the Genomic and Per...
	11.5 Defining Opportunities and Threats When Implementing Genomic and Personalized Medicine
		11.5.1 Opportunities
		11.5.2 Obstacles and Threats
	11.6 Concluding Remarks
	Competing Interests
	Acknowledgments
	References
	Further Reading
12 Health-Care Professionals’ Awareness and Understanding of Genomics
	12.1 Introduction
	12.2 Research on Health-Care Professionals’ Knowledge and Understanding of Genomics
		12.2.1 Studies in Individual Countries
		12.2.2 The Ubiquitous Pharmacogenomics: A European Initiative
	12.3 Studies With Oncologists
	12.4 Nurses’ Perceptions and Understanding of Genomics
	12.5 A Multidemographic Perspective
	12.6 Educational Challenges in Implementing Genomic Medicine
	12.7 Conclusion
	References
	Further Reading
13 “Genethics” and Public Health Genomics
	13.1 Introduction to Ethical Issues in Public Health
	13.2 Introduction to Ethical, Legal, and Social Issues in Genetics and Genomics
	13.3 Can Genomics Improve Public Health?
		13.3.1 Genomic Sequencing in Diagnosis
		13.3.2 Genomic Screening
		13.3.3 Clinical Utility
		13.3.4 Genome Sequencing in the Context of Reproduction
		13.3.5 Germline Genome Editing
			13.3.5.1 Context 1: Using germline genome editing to avoid having a child with disease in a situation where there is no cha...
			13.3.5.2 Context 2: Using germline genome editing to avoid having a child with a disease in a situation where, in theory, s...
			13.3.5.3 Context 3: Using germline genome editing to prevent disease/enhance
	13.4 Conclusion
	Acknowledgments
	References
14 Legal Aspects of Genomic and Personalized Medicine
	14.1 Introduction
	14.2 Genomics Legislation in the United States of America
	14.3 Genomics Legislation in the European Union
		14.3.1 Estonia
		14.3.2 Ireland
		14.3.3 Sweden
		14.3.4 Latvia
		14.3.5 Iceland
		14.3.6 Lithuania
		14.3.7 The Netherlands
		14.3.8 Norway
		14.3.9 Finland
		14.3.10 Luxembourg
		14.3.11 France
		14.3.12 Portugal
		14.3.13 Slovenia
		14.3.14 Spain
		14.3.15 Italy
		14.3.16 Croatia
		14.3.17 Greece
		14.3.18 Cyprus
		14.3.19 Romania
		14.3.20 Austria
		14.3.21 Bulgaria
		14.3.22 Hungary
		14.3.23 Czech Republic
		14.3.24 Germany
		14.3.25 Switzerland
	14.4 Genomics Legislation in Asia
		14.4.1 Singapore
		14.4.2 China
	14.5 Genomics Legislation in the Middle East
		14.5.1 United Arab Emirates
		14.5.2 Lebanon
		14.5.3 Qatar
	14.6 Discussion
	14.7 Conclusions
	References
	Further Reading
15 Genomics, The Internet of Things, Artificial Intelligence, and Society
	Abbreviations
	15.1 Introduction
		15.1.1 A New Relationship for Science and Society
	15.2 Postgenomic Technologies and Society
		15.2.1 The Anticipated and the Unanticipated
		15.2.2 Genomics Meets the Internet of Things and Artificial Intelligence—Toward a “Quantified Planet”
	15.3 Technology Policy Design
	15.4 Conclusion and Outlook
	Acknowledgments
	References
	Further Reading
16 Economic Evaluation of Genomic and Personalized Medicine Interventions: Implications in Public Health
	16.1 Introduction
	16.2 Pharmacogenomics, Personalized Medicine, and Health Economics
	16.3 Economic Evaluation: Terminology and Concept
	16.4 Methods Used in Economic Evaluation
		16.4.1 Cost-Minimization Analysis
		16.4.2 Cost-Effectiveness Analysis
		16.4.3 Cost-Utility Analysis
		16.4.4 Cost-Benefit Analysis
		16.4.5 Cost-Threshold Analysis
	16.5 Economic Evaluation in Genomic and Personalized Medicine
	16.6 Examples of Economic Evaluation in Genomic and Personalized medicine
		16.6.1 Using Pharmacogenomics to Prevent Adverse Drug Reactions
		16.6.2 Between Adverse Drug Reactions and Efficacy
	16.7 Cost-Effectiveness Analysis in Genomic Medicine and the Developing World
	16.8 Models for Economic Evaluation in Genomic Medicine
	16.9 Conclusions and Future Challenges
	Acknowledgments
	References
17 Pricing, Budget Allocation, and Reimbursement of Personalized Medicine Interventions
	17.1 Introduction
	17.2 Institutions Involved in Pricing and Reimbursement
	17.3 Coverage, Pricing, and Reimbursement Strategies for Genomic Tests
	17.4 Components of the Proposed Strategy for Pricing and Reimbursement in Personalized Medicine
		17.4.1 Universal Access to Essential Genomic Testing for All, at Acceptable Prices for the Health System
		17.4.2 Sufficient Regulation to Ensure Safety, Efficacy, Quality, Fairness, and Solidarity, While Allowing Space for Innova...
		17.4.3 Appropriate Use of Genomic Tests and Information by Physicians, According to Patients’ Needs and Clinical Utility/Ac...
		17.4.4 Investment in Human Resources and Research Into the Field of Personalized Medicine, Evaluation of Novel and Existing...
	17.5 Public Health Policy Concerns
	17.6 Incentives for Personalized Medicine
	17.7 Conclusion and Future Perspectives
	References
18 Genetic Counseling
	18.1 Introduction and Background
	18.2 Fundamentals of Genetic Counseling
		18.2.1 Access to Genetic Counseling
		18.2.2 Tools of Practice
		18.2.3 Patient Education
		18.2.4 Complete Disclosure of Information
		18.2.5 Shared Decision-Making
		18.2.6 Psychosocial Assessment
		18.2.7 Confidentiality, Privacy, and Data Sharing
	18.3 Genetic Counseling in Population Health Initiatives
		18.3.1 Clinical Genome Resource
		18.3.2 Genomic Sequencing in Healthy Populations
		18.3.3 Cascade Testing: Reaching Out to At-Risk Family Members
		18.3.4 Lessons Learned
	18.4 Implications for Public Health Genomics
	References
19 Defining Genetic-Testing Delivery and Promotional Strategies for Personalized Medicine
	19.1 Introduction
	19.2 Genetic-Service Delivery Models
		19.2.1 Genetic Services Provided by Geneticists
		19.2.2 Genetic Services as a Part of Primary Care
		19.2.3 Genetic Services Provided by the Medical Specialist
		19.2.4 Genetic Services Integrated Into Large-Scale Population-Screening Programs
		19.2.5 Genetic Services Provided Using the Direct-to-Consumer Model
	19.3 Marketing in Public Health
	19.4 Marketing in Genetic-Testing Services
	19.5 Defining the Marketing Strategy for Genetic-Testing Services
		19.5.1 Target Audience
		19.5.2 The Marketing Mix
		19.5.3 Diversity
		19.5.4 Confidence
		19.5.5 Strengths, Weaknesses, Opportunities, and Threats Analysis
			19.5.5.1 Strengths
			19.5.5.2 Weaknesses
			19.5.5.3 Opportunities
			19.5.5.4 Threats
		19.5.6 Political, Economic, and Social Policies, Technological Developments, Legislation, and the Environment Analysis
	19.6 Defining the Landscape of Genetic Testing in Various Countries
		19.6.1 Overview of Genetic Testing Services in Malaysia
		19.6.2 Genetic-Testing Services in Greece
	19.7 Conclusion and Perspectives
	Acknowledgment
	References
	Further Reading
20 Regulatory Aspects of Genomic Medicine and Pharmacogenomics
	20.1 Introduction: Public-Health System and Regulation
		20.1.1 Public Health and the Need for Regulation Thereof; Issues of Agency and Confidence
		20.1.2 Health Interventions and Need for Regulation Thereof
		20.1.3 Bridging Regulation With Medical Practice
	20.2 Regulation of In Vitro Diagnostic Medical Devices
		20.2.1 General Regulatory Requirements
		20.2.2 In Vitro Diagnostic Medical-Device Regulation in the United States and European Union
		20.2.3 Companion Diagnostic In Vitro Medical Device Regulation
		20.2.4 Companion Diagnostics and Biomarkers
	20.3 Genomic Information and Regulation
		20.3.1 General Aspects
		20.3.2 Aspects and Applications of Individualized Evidence-Based Patient Benefit
		20.3.3 The Case for Cancer and Further Ramifications of Genomic Medicine
		20.3.4 General Considerations for Regulatory Evolution Following Genomic Medicine
	20.4 Conclusion and a Look Ahead
	References
21 Genomic Medicine in Emerging Economies
	21.1 Introduction
	21.2 From Sanger Sequencing to Next-Generation Sequencing and Nation-Wide Genomic Programs
	21.3 Capacity Building and Cost of Setting Up Sequencing Centers
	21.4 Lack of Diversity on International Databases
	21.5 Parachute Research
	21.6 Education and Capacity Building
	21.7 Fast-Second Winner Model
	21.8 Health Biotechnology in Latin America
	21.9 Genomics in Africa
	21.10 Global Initiatives
	References
Index