Handbook of Genomics and the Family (eBook)

Kenneth P. Tercyak, PhD is an associate professor in the Division of Health Outcomes and Health Behaviors of the Department of Oncology and in Pediatrics at the Georgetown University Medical Center in Washington, DC. He received his bachelor of arts degree in psychology from the University of Pennsylvania, and doctor of philosophy in clinical psychology from the University of Florida’s College of Public Health and Health Professions.Dr. Tercyak’s research has focused on cancer prevention and control among children, adolescents, and families. This includes investigations of the social and behavioral aspects of genetic testing for hereditary cancer syndromes among parents, developing and testing strategies for informed decision making and communication support in cancer genetics, and evaluating long-term outcomes among children growing-up in environments affected by familial cancer. Dr. Tercyak’s other investigations have included a focus on biopsychosocial influences on youth smoking adoption, pediatric cancer survivorship, adolescent health promotion, and predictive testing for common disease risk. He has received continuous funding by the National Institutes of Health since 1998, including a National Research Service Award and Research Career Development Award from the National Cancer Institute, and funding from the National Human Genome Research Institute’s Ethical, Legal, and Social Implications research program and the Division of Cancer Control and Population Sciences at the National Cancer Institute.Dr. Tercyak’s scholarly contributions consist of more than 75 journal articles and book chapters. He has delivered invited presentations at a number of scientific organizations, including the American Society of Human Genetics, the Dana-Farber Cancer Institute, and St. Jude Children's Research Hospital.Dr. Tercyak is a Full Member of the Division of Population Sciences and the Jess and Mildred Fisher Center for Familial Cancer Research at the Lombardi Comprehensive Cancer Center at Georgetown. He is also a member of the Behavioral Medicine Study Section of the National Institutes of Health, and former member of the psychosocial peer review committees of the American Cancer Society and Susan G. Komen for the Cure Foundation; he has served as a grant reviewer for other National Institutes of Health study sections and special emphasis panels and international research organizations as well. Dr. Tercyak is a reviewer for a number of professional journals. Currently, he is serving a term as Associate Editor for prevention science at the Journal of Pediatric Psychology and is a member of the incoming editorial board at Health Psychology.

Preface 6
References 10
Acknowledgments 14
Contents 15
Introduction 18
About The Editor 20
Contributors 22
Part I Introduction to Genomics 25
1 Key Concepts in Human Genomics and Epidemiology 26
Introduction 26
The Human Genome Project 28
Neural Tube Defects 30
The Etiology of NTD Involves Environmental and Genetic Factors 31
Genetic Causes of NTD 32
Interrelationship of Folic Acid and Genetics in NTD 33
Environmental Causes of Neural Tube Defects 35
Environmental, Dietary, and Genetic Interactions in NTD 36
Childhood Cancer 37
The Etiology of Childhood Leukemia Involves Environmental and Genetic Factors 38
Genetic Causes of Childhood Leukemia 38
Environmental Factors and Childhood Leukemia 39
Environmental and Genetic Interactions in Childhood Leukemia 41
Conclusions: Impacts Of Expanding Research In Genomics And ChildrenS Health 43
References 10
2 Psychological Genetics: Understanding the Natureof Psychological Differences Through Etiology 55
Introduction 55
Principles Of Behavioral Genetic Design: The Coinheritance Of Genetic And Psychological Characteristics 56
Types Of Behavioral Genetic Designs 58
Generalizations To Be Made About Genes And Human Behavior 62
Delineating Psychological Constructs: The Interdependence Of Psychological And Genetic Inquiry 66
Emerging Issues And The Future Of Psychology And Genetics 73
References 74
Part II CrossCutting Issues in Children and Families 78
3 Understanding Gene, Environment, and Gene Environment Interaction Effects: The Exampleof Childhood Externalizing Disorders 79
Introduction 79
Family Studies 82
Twin Studies 83
Adoption Studies 86
Combination Studies 88
GeneEnvironment Correlation And Interaction 91
Conclusions And Future Directions 97
References 99
4 Process in Genetic Counseling: Considerations for Children and Their Families 107
Introduction 107
Role Of Genetic Counseling 108
Structure of Medical Genetics Counseling Sessions 109
Comprehension and Family Meaning of Genetic Health Information 110
Intrafamilial Relationships and Communication Dynamics 111
Empowering Families 113
Special Considerations For Children 114
Genetic and Genomic Testing 114
Ethical Concerns About Testing 115
Considerations for Communicating Genetic and Genomic Information to Children 117
Increasing The Complexity: Integrating Genomic Risk Information 120
Genomic Testing and Risk Information for Children and Families 120
New Challenges 121
Counseling About Genomic Health Information 122
Conclusion 123
References 123
5 Genomics and the Family: Integrative Frameworks 128
Introduction 128
Importance Of Theory And Theorizing 129
Case Study 130
Individual And Family Factors That Influence Adaptation 131
Factors That Influenced Adaptation In JenniferS Family 132
RiskResistance Adaptation Models 134
Risk Factors 135
Resistance Factors 135
Adjustment/Adaptation Outcomes 136
Resiliency Model Of Family Stress, Adjustment, And Adaptation 136
Family Demands 138
Family Types 138
Family Resources 139
Family Appraisal 140
Family Problem-Solving Communication and Coping 140
Family Management Style Framework 141
Definition of the Situation 144
Management Behaviors 145
Perceived Consequences 146
Family Management Style 146
Family System Genetic Illness Model 147
Psychosocial Typology of Genomic Disorders 148
Nonsymptomatic Time Phases of Genomic Disorders 149
Relationship Between Guiding Framework And Plan Of Care 151
Conclusion 152
References 153
6 Potential Impact of Genomic Information on Childhood Sibling Relationships 159
Introduction 159
Research Background and Scope of the Problem 160
A Comparison of Disorders: Autosomal and X Linked 163
Siblings of Children with AT 163
Study of Siblings of Children with AT 164
Understanding of Genetic Information and Perception of Carrier Status 164
Family Communication 165
Sibling Guilt 165
Case Example -- Sibling of Individuals with AT 166
Siblings of Children with XSCID 166
Study of Siblings of Children with XSCID 167
Understanding of Genetic Information and Perception of Carrier Status 167
Family Communication 168
Sibling Relationships 168
Sibling Guilt 168
Parental Mourning 169
Case Example -- Sibling of Males with XSCID 169
Comparisons Between CF, AT, and XSCID: Key Similarities and Differences 169
Siblings as Bone Marrow and Stem Cell Donors 170
Case Example 172
Preparation: Assessment and Interventions 173
Pre-implantation Genetic Diagnosis 173
Summary and Conclusion 174
References 175
7 Family Communication of Genomic Information 180
Introduction 180
Family Communication as Process 183
Communication Barriers and Facilitators 185
Disease Factors 185
Inheritance Pattern 185
Disease Severity and Preventability 187
Certainty of Test Results 187
Individual Factors 188
Emotions 188
Coping Strategies 188
Family Factors 189
Type of Relationship 189
Family Communication Between Parents and Children 189
Family Communication Style 191
Family Myths About Inheritance 192
Sociocultural Factors 192
Gender 192
Concerns About Genetic Discrimination 193
Culture 194
Functions of Communication 195
To Convey Information 195
To Facilitate Coping 196
To Create or Maintain Identity 196
Future Directions 197
References 201
8 Conveying Genetic Risk to Teenagers 207
Illness Perceptions: The Role Of Causality 208
Challenges Of Conveying Risk To Youth 209
Understanding Of And Outcomes Related To Risk Communication 212
Probabilistic Approaches To Conveying Risk: The Role Of Numeracy 214
Strategies In The Use Of Numerical Data To Convey Probabilistic Risk Information 216
The Use Of Graphical Displays As Adjuncts To Conveying Numerical Probabilistic Risk Information 219
Incorporation Of Probabilistic Information With Other Risk Communication Approaches 220
Suggested Areas For Future Research 224
Concluding Statements 227
References 228
Part III Genes, Behavior, and Health 234
9 Prenatal Screening and Diagnosis 235
Introduction 235
History And Current Status Of Prenatal Screening And Diagnosis 236
Genetic Carrier Screening 237
Non-invasive Screening in Pregnancy 238
Invasive Diagnostic Testing 239
Factors That Impact Whether To Undergo Prenatal Testing 240
The Genetic Counseling Process 245
Recieving Bad NewsAnd The Subsequent Decision Making 246
Psychological Reactions to Abnormal Prenatal Diagnosis 246
The Decision to Continue the Pregnancy 247
The Decision to Terminate the Pregnancy 248
Professional Issues For Future Consideration 248
Conclusions 249
References 250
10 Single Gene Disease Risk 255
Introduction 255
Patient Adaptation 257
Parent And Family Adaptation 259
Psychological Implications for Mothers 260
Impact on Reproductive Decision Making 260
Implications Of Delayed Diagnosis 261
Newborn Screening 263
Medical and Developmental Outcome for the Child 265
Psychosocial Implications for Family 267
Psychosocial Implications for Patients 269
Implications for Reproductive Decision Making 271
Future Challenges 271
Future Directions 273
References 276
11 Hereditary Cancer Risk 281
Hereditary Cancers, Cancer Syndromes, And Conditions Featuring Malignancies Affecting Children 282
Nonsyndromic Cancers 282
Chromosome Instability Syndromes 289
Other Genetic Conditions with Malignancy Risks 289
Hereditary Cancer Syndromes Affecting Children 291
Hereditary Cancer Syndromes Generally Manifesting In Adulthood 292
Psychosocial Research 293
Childhood Onset 293
Adult Onset 296
Predictive Genetic Testing In Children 299
Future Directions 301
References 301
12 Type 1 Diabetes Risk 306
The Genetics and Natural History of Type 1 Diabetes 307
Genetic Testing for T1D: Ethical Issues 309
Psychosocial Impact of T1D Genetic Testing 309
Cognitive Impact of T1D Genetic and ICA Testing: Understanding T1D Risk 310
Emotional Impact of T1D Genetic and ICA Testing: Anxiety, Worry, and Depression 312
Behavioral Impact of T1D Genetic and ICA Testing: Surveillance and Disease Prevention 317
Reactions to Study Participation: Satisfaction and Burden 317
Implications for Patient Care, Research, and Health Policy 318
Patient Care 318
Future Research 319
Health Policy 320
References 321
13 Cardiovascular Disease Risk 325
Introduction 325
Background And Significance: Atherosclerosis And Its Risk Factors: The Precursors To Cad 325
Genetics Of Lipid Metabolism 327
Obesity And The Risk For Heart Disease 329
Environmental Factors Of Cardiovascular Disease Risk 331
Participation in Physical Activity 331
Dietary Trends 331
Tobacco Use 333
Children/Adolescent/Family Social, Psychological, And Behavioral Issues 333
Conclusions 334
References 335
14 Obesity Risk 340
Introduction 340
Energy Balance And The Development Of Childhood Obesity 341
Familial Transmission Of Obesity 341
Heritability Of Obesity 342
Can Obesity-Promoting Eating Behaviors And Preferences Be Inherited 343
High-Risk Research Designs To Study Eating Traits Contributing To Childhood Obesity 343
Overview of High-Risk Design 343
The Infant Growth Study 344
Twins Early Development Study )TEDS) 346
Specific Genetic Associations With Obesity Risk And Eating Behavior 347
Emotional Eating And Obesity 347
Translating Genetic Information About Obesity Risk Into Treatment And Prevention: The Case Of Genetic Testing 348
Conclusions 349
References 350
15 Tobacco and Alcohol Use Behaviors 355
Background 355
Epidemiology 355
Within-Individual Clustering of Disorders 356
Family Effects and Familial Clustering 356
Morbidity, Mortality, and Costs to Society 357
Summary 357
Approaches to Gene Discovery 358
Heritability 358
Approaches in the Search for Genetic Contributors 359
Linkage Approach 359
Candidate Gene Approach 360
Whole Genome Association Approach 360
Summary of Major Findings 361
Linkage Studies of Alcohol and Tobacco Phenotypes 361
Association (Candidate Gene and Whole Genome Association) Studies of Alcohol and Tobacco Phenotypes 361
Alcohol and Acetaldehyde Dehydrogenase Genes 362
-Aminobutyric Acid Receptor Genes 363
Nicotinic Receptor Genes 364
Summary 366
Promise of Future Genetic Findings 366
Treatment Implications 366
Prevention/Genetic Susceptibility Testing 368
Unintended Consequences 369
Conclusion 369
References 370
16 Childhood Neuropsychiatric Risk 378
Introduction 378
Background and Significance 379
Attention Deficit Hyperactivity Disorder (ADHD) 381
Family Studies 381
Candidate Genes 381
Genomic Studies 382
Gene--Environmental Interactions 382
ADHD: Developmental Phenotype 384
Pharmacogenetics 384
Summary and Psychosocial Implications 386
Obsessive-Compulsive Disorder (OCD) 386
Family Studies 386
Candidate Genes 386
Genomic Studies 387
Gene--Environmental Interactions 387
OCD Developmental Phenotype 388
Pharmacogenetics 388
Summary and Psychosocial Implications 388
Schizophrenia 388
Family Studies 389
Candidate Genes 389
Genomic Studies 390
Developmental Phenotype 391
Gene--Environmental Interactions 391
Pharmacogenetics 391
Summary and Psychosocial Implications 392
Pervasive Developmental Disorders 392
Family Studies 393
Candidate Genes 393
Genomic Studies 394
Gene--Environmental Interactions 394
Summary and Psychosocial Implications 394
Forecasting 395
Promises of Genetic Advances 395
Ethical Considerations 395
Translation 396
Genetic Counseling 396
Genetic Testing 397
Pharmacogenetic Testing 398
Privacy of Genetic Information 398
Conclusion 399
References 399
17 Genomic Risk Information for Common Health Conditions: Maximizing Kinship-Based Health Promotion 415
Genetic Risk Information: Tools of Today and Tomorrow 418
Family Health History 418
Genetic Susceptibility Testing for Common Health Conditions 420
Opportunities and Challenges Raised by Genetic Risk Assessments 421
Genetic Risk Information as Part of Kinship-Based Health Promotion Efforts 423
Considering Naturally Occurring Risk Synergies 424
Future Research Needs 428
Capitalizing on the Kinship Social Structure to Promote Health 430
Evaluation of Genetics-Informed Intervention Programs to Improve Health 431
Development of Statistical Methods for Kinship Networks 432
Conclusions 434
References 435
Part IV Emerging Issues 442
18 Pediatric Pharmacogenomics 443
Background 444
Pharmacogenetics in Asthma Treatment 447
Asthma Steroid Pharmacogenetics 447
-Adrenergic Receptor Gene in Asthma Treatment 448
Leukotriene Response in Asthma Treatment 449
Pharmacogenetics in Attention-Deficit Hyperactivitiy Disorder 450
Pharmacogenetics in Childhood Leukemia 451
Translation and Challenges in Pharmacogenetics 452
Gene Therapy 454
Applying Pharmacogenomics in Medication Management for Pediatric Chronic Conditions: Psychological Aspects 455
Involving Families in Decision Making Regarding Personalized Treatment 455
Engaging Families in Adherence Promotion 456
Evaluating Treatment Adherence in Research and Clinical Care 457
Conclusion 457
References 458
19 Informed Consent and the Protection of Human Subjects in Genomic Research with Children and Families 463
Pediatric Research Initiatives 464
The Bioethics of Protection of Children in Clinical Research 465
Historical Perspectives 466
Enrollment of Children in Research 466
The Child's Role in the Research Enrollment Process 466
Parental Decision Making and Research 469
Current State of Pediatric Genetic Testing Under Research Initiatives 471
Newborn Screening 471
Genetic Studies in Symptomatic Children 472
Genetic Studies in Children with No Genetic Risk Factors 473
Ethical Issues About Genetic Testing in Children 473
Research into Risks Involved in Genetic Assessment in Children 475
Factors Affecting Parental Enrollment Decisions 477
Genetic Testing of Children 478
Familial Sharing of Genetic Information 478
Discussion 478
Conclusion 484
References 484
20 Ethical, Legal and Social Issues in the Genetic Testing of Minors 490
Introduction 490
Ethical Standards For Genetic Testing 493
Children and Adults 493
Special Standards for Adolescents? 495
Balancing of Ethical Principles 496
The Entanglement of Family and Child Benefits 496
Justice 497
Informing About Genetic Risks 498
Newborn Screening 498
Carrier Testing And Carrier Screening 501
Carrier Testing of Individual Children 503
Carrier Screening Programs for Minors 506
Ethical Problems In Predictive Genetic Testing For Diseases With Childhood Onset Where No Treatment Or Prevention Exists 508
Ethical Problems In Predictive Testing Of Children For Diseases With Childhood Onset For Which Medical Interventions Are Available 509
Predictive Testing Of Minors For Adult-Onset Diseases 511
The Ethical Dilemma 511
Conflicting Interests of Parents and Their Children 517
Future Developments And Conclusions 518
References 519
21 Guidelines and Policies on Genetic Testing in Children and Families 527
Background 528
Genetic Testing in Children for Diagnostic Purposes and Medical Management 529
Genetic Assessment Through Newborn Screening 530
Carrier Screening During Childhood and Within Families 532
Presymptomatic and Susceptibility Testing for Inherited Disease and Disorders 533
Genomic Testing for Common, Complex Disorders: Considerations for the Future 534
Research And Empirical Literature On Pediatric Genetic Testing 535
Reasons for Genetic Testing of Minors 535
Reasons for Deferring Genetic Testing of Children 536
Outcomes of Genetic Testing in Children 536
Attitudes Toward Genetic Testing 537
Us Task Forces And Committees Assessing Genetic Testing 537
National Institutes of Health -- Department of Energy Working Group on Ethical, Legal, and Social Implications of Human Genome Research 537
Institute of Medicine 538
National Institutes of Health -- Department of Energy (NIH-DOE) Task Force on Genetic Testing 541
Secretary's Advisory Committee on Genetic Testing (SACGT) 541
Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS) 542
Existing Guidelines And Practice Statements 543
Oversight And Regulation Of Genetic Testing 544
Oversight of Laboratories Conducting Genetic Testing 544
Oversight and Support for Programs Conducting Pediatric Genetic Testing 546
Legislative Efforts and Regulatory Actions 548
Challenges 549
Conclusions 552
Appendix 553
Case Scenario 1 553
Pediatric Genetic Testing for Diagnostic and Medical Management Purposes 553
Case Scenario 2 554
Carrier Testing 554
Case Scenario 3 555
Presymptomatic Testing for Disease Potentially Presenting During Childhood 555
Case Scenario 4 556
Presymptomatic Genetic Testing for Adult-Onset Disease During Childhood 556
Case Scenario 5 558
Genetic Testing for Obesity: A Challenge for the Future 558
References 559
22 Training, Practice, and Collaboration:New Opportunities for Pediatric Psychologyand Genomic Medicine 562
Introduction 562
How is Genetic Information Different 564
How is Genetic Information Regarding Children Different 566
The Roles for Pediatric Psychologists 568
What Competencies are Needed 569
Basic Genetics Concepts and Tools 570
Family History Taking and Pedigrees 571
Genetics Resources 572
Ethical Issues Concerning Children and Genetic Testing 572
Ethical Considerations in Pediatric Clinical Research 574
Biobanks and Children 575
Conclusions 575
References 576
23 Public Health Genomics 579
What is Public Health Genomics 580
Disclosure of Genetic Risk Information and Associated Health Decisions 581
Providing Informed Consent/Assent and the Need to Build our Knowledge Base 585
Impact of Early Environment on Gene Expression and Overall Health 586
Improved Phenotypes and Exposure Measurements 588
An Example: Pediatric Lipid Screening 590
Conclusion 591
References 592
Subject Index 596