Psychiatric Genomics presents and synthesizes available knowledge in the field of psychiatric genomics, offering methodologies to advance new research and aid clinical translation. After providing an introduction to genomics and psychiatry, international experts discuss the genomic basis of schizophrenia, bipolar disorder, depression, personality disorders, anxiety disorders, addictions, eating disorders, and sleep disorders, among other disorders. In addition, recommendations for next steps in clinical implementation and drug discovery are discussed in-depth, with chapters dedicated to pharmacogenomics and antipsychotics, antidepressants and mood stabilizers, adverse drug reactions, implementation of pharmacogenomics in psychiatric clinics, and ethical issues.

Finally, methods sections provide a solid grounding in research approaches and computational analytics, from using animal models in psychiatric genomics and accessing biobanks, to employing computational analysis, genome-wide association studies (GWAS), brain pathophysiology, and endophenotypes in psychiatric research.

Cover image
Title page
Table of Contents
Copyright
Dedication
List of contributors
About the editors
Preface
Chapter 1. Genomics and psychiatry: a historical overview
Abstract
Introduction
The Middle Ages
The 18th century
Era of enlightenment
The 19th century
The 20th century
Twin studies
Adoption studies
Modern family studies
DNA sequencing
21st century
Human genome project
Genome-wide association studies
Consortia
Lessons learned from history
References
Chapter 2. Schizophrenia genomics
Abstract
Introduction
Schizophrenia heritability
Molecular genetics before genomics
Defining the phenotype
Genome-wide association studies
Rare structural risk variants
Genome sequencing studies
Lessons learned from schizophrenia genomics
Conclusion
References
Chapter 3. Genetics of bipolar disorder
Abstract
Introduction
Family and adoption studies
Genome-wide association studies
GWAS in BD
Genetic architecture of BD
From genetic loci to disease mechanisms
Rare genetic variants in BD
Potential clinical implications of BD genetics
Conclusion
Acknowledgments
Competing financial interests
References
Chapter 4. Genetics of depression
Abstract
Genetic factors affecting the onset of depression
Conclusions
References
Chapter 5. Genetics of personality disorders
Abstract
Introduction
First evidence of genetic predisposition in personality disorders
Genome-wide associations studies in personality disorders
Conclusions
References
Chapter 6. Genomics and epigenomics of anxiety and obsessive-compulsive disorders
Abstract
Clinical genetics, molecular genetics, gene-environment interactions and epigenetics of anxiety disorders
Molecular genetics
Gene environment interactions and epigenetics
Molecular genetics
Gene environment interactions and epigenetics
Therapy (epi)genetics of anxiety and OCDs
Conclusion
References
Chapter 7. Neurogenetics of alcohol use disorder a subset of reward deficiency syndrome: candidate genes to be or not to be?
Abstract
Introduction a historical overview
Finding the first alcohol gene
Understanding polygenic inheritance of alcoholism and links to opioids
GARS case controls and targeted endophenotypes for alcohol abuse and alcoholism
Importance of genome wide association studies: convergence to candidates
Conclusion
Acknowledgments
Author contribution
Funding
Conflict of interest
References
Chapter 8. Pharmacogenomics and antipsychotics: efficacy and adverse drug reactions
Abstract
Introduction
Pharmacogenetics of antipsychotics metabolizing enzymes and drug targets
Pharmacogenes involved in antipsychotic metabolism and transport
Pharmacogenomics of antipsychotic efficacy
Candidate gene studies of treatment response
Genomic studies of antipsychotic efficacy
Epigenetics of treatment response
Pharmacogenetics of antipsychotic-induced adverse drug reactions
Tardive dyskinesia
Clozapine-induced agranulocytosis and neutropenia
Antipsychotic-induced weight gain
Pharmacogenetic-based treatment guidelines for antipsychotics
Pharmacogenomic testing
Clinical implementation studies
Conclusions
References
Chapter 9. Pharmacogenomics and antidepressants: efficacy and adverse drug reactions
Abstract
Financial disclosures (last 3 years)
Cautionary statements
Safety versus efficacy, and pharmacokinetics versus pharmacodynamics
Pharmacokinetic pharmacogenomics and efficacy
Pharmacodynamic pharmacogenomics and efficacy
Antidepressant efficacy trials using combinatorial pharmacogenomic panels
Clinical implications and future directions
Conclusions
References
Chapter 10. Pharmacogenomics and mood stabilizers: efficacy and adverse drug reactions
Abstract
Introduction
Pharmacogenomics of lithium
Pharmacogenomics of other mood stabilizers
Discussion
References
Chapter 11. Balancing prevention and respect: the ethical stakes of a psychiatric genomics lens for mental disorder and intellectual disability
Abstract
Introduction
Conceptual framing and ethical orientation: points of divergence
Challenging projections of suffering
Responding to the ethical stakes
Conclusion
Acknowledgment
References
Chapter 12. Genetic animal models for psychiatric disorders
Abstract
Genetic evidence, epidemiology, and genetic animal models
Schizophrenia
Bipolar disorder
Major depressive disorder
Conclusion
References
Chapter 13. Psychiatric genomics: brain pathophysiology and genetic factors
Abstract
Introduction
Autism spectrum disorders
Schizophrenia
Major depressive disorder
Panic disorder
Conclusions
References
Chapter 14. Integration with systems biology approaches and -omics data to characterize risk variation
Abstract
Introduction
Functional annotation of noncoding regions
Context-specific genetic regulation
Mapping GWAS to QTLs
Multi-QTL methods
Annotation of variants to gene pathways
Conclusion/Future Directions
References
Chapter 15. Usage of biobank data for psychiatric genomics and promotion of precision psychiatry
Abstract
Introduction to biobanks
Psychiatric genomics in a biobank setting
Contextualizing the limitations of biobanks for psychiatric genomics
Algorithmic phenotyping
Evaluation of algorithmic phenotyping
Chart review
Automated phenotyping
Major impact of biobanks on psychiatric genomics research
Applications to genome-wide association studies
Phenome-wide and lab-wide association studies
Practicing the implementation of precision psychiatry
Ethical considerations
Future directions
References
Chapter 16. Shared heritability among psychiatric disorders and traits
Abstract
Heritability
Shared heritability, genetic overlap, and pleiotropy
Evaluating genetic overlap
Rare variant genetic overlap
Implications for psychiatry
Conclusion
Acknowledgments
Competing financial interests
References
Chapter 17. Endophenotypes in psychiatric genomics: a selective review of their status and a call to action
Abstract
Introduction and context: The endophenotype construct
Progress in identifying genomic endophenotypes
Questioning the clinical utility of endophenotypes
Advancing a dimensional understanding of psychopathology
Clinical translation of endophenotypes
Race and racism in psychiatric genomics
Conclusions
Acknowledgment
References
Index