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Monograph 20: Phenotypes and Endophenotypes
Foundations for Genetic Studies of Nicotine Use and Dependence

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1. Download the entire monograph (13,232 kb)
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3. Download only the chapters you are interested in (see below)
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Entire Monograph (13,232 kb)
Navigate within the PDF by clicking on the bookmarks on the left to jump to the appropriate chapter. Or, click on the search button in the top toolbar (binoculars icon) and enter a keyword or phrase in the text box. Click on the links in the results window to jump to the appropriate page.

Table of Contents:

• Figures and Tables (51 kb)
• Foreword (22 kb)
• Message from the Series Editor (29 kb)
• Acknowledgments (48 kb)
• Acronyms and Abbreviations (37 kb)

Part 1 – Introduction

• Chapter 1
  Overview and Conclusions (110 kb)
  • Introduction
  • About the Monograph
  • Major Accomplishments
  • Major Conclusions
  • Chapter Summaries and Conclusions
  • References


• Chapter 2
  Status of Genetic Studies of Nicotine Dependence
  (363 kb)
  • Introduction
  • Historical Perspective of Genetic Research on Nicotine Dependence
  • Nicotine Dependence: A Construct in Need of Refinement
  • Nicotine-Dependence Phenotypes: A Framework
  • Gentic Epidemiological Concepts and Their Implications for Studying Nicotine Dependence
  • Summary of Selected Biometric and Measured Genetic Studies of Nicotine Dependence
  • Issues in Communication of Genetic Findings
  • Summary
  • References

Part 2 – Theoretical Considerations

• Chapter 3
  The Nicotine-Dependence Phenotype: Translating Theoretical Perspectives and Extant Data into Recommendations for Genetic Mapping (448 kb)
  • Introduction
  • Construct Validation
  • Distal Measures of Dependence
  • New Directions for Phenotypic Research: Beyond Distal Measures
  • Summary
  • Conclusions
  • References


• Chapter 4
  Mouse Models and the Genetics of Nicotine Dependence (1,605 kb)
  • Introduction
  • Nicotinic Receptor Functional Diversity
  • Routes of Nicotine Administration: Interaction of the Drug with Physiological Systems
  • The Mouse Model of Nicotine Dependence
  • Nicotine and Behavioral Changes
  • Nicotine and Reward
  • Tolerance
  • Additional Directions for Research on the Nicotine-Dependence Phenotype in Mice
  • Summary
  • Conclusions
  • References

Part 3 – Developmental Trajectories of Tobacco Use and Their Relation to Tobacco Dependence

• Chapter 5
  Developmental Trajectories of Cigarette Smoking from Adolescence to Adulthood (285 kb)
  • Introduction
  • A Developmental Psychopathology Perspective: Studying Multiple Trajectories over Time
  • Empirically Identified Trajectories of Adolescent Smoking
  • Statistical Models for Evaluating Alternative Developmental Phenotypes of Smoking Behavior
  • An Empirical Example: Trajectories in the Indiana University Smoking Survey
  • Future Research Directions
  • Summary
  • Conclusions
  • References


• Chapter 6
  Genetic Modeling of Tobacco Use Behavior and Trajectories (484 kb)
  • Introduction
  • Methodological and Conceptual Issues
  • Statistical Framework
  • Review of Genetic Studies of Smoking
  • Item Response Theory Approach: Application to Virginia Twin Registry Data
  • Limitations
  • Summary
  • Conclusions
  • References


• Chapter 7
  Trajectories of Tobacco Use from Adolescence to Adulthood: Are the Most Informative Phenotypes Tobacco Specific?
  • Introduction
  • Importance of Studying Substance-Use Comorbidity
  • Common Versus Specific Liability to Substance-Use Disorders
  • Review of Trajectory Literature
  • Associations between Substance-Use Trajectories and Other Substance Involvement
  • Modeling Conjoint Trajectories of Substance Use
  • Empirical Example of Modeling Co-Occurring Courses of Substance Use
  • Method
  • Results
  • Summary
  • Conclusions
  • References

Part 4 – Endophenotypes

• Chapter 8
  Endophenotypes for Nicotine-Dependence Risk at or before Initial Nicotine Exposure (352 kb)
  • Introduction
  • Endophenotypes
  • Smoking Initiation and Progression Risk: Examination of Key Candidate Psychological Domains
  • Initial Nicotine Exposure Response: Conceptual Framework and Candidate Endophenotypes
  • Discussion of Future Directions
  • Summary
  • Conclusions
  • References


• Chapter 9
  Nicotine-Dependence Endophenotypes in Chronic Smokers (389 kb)
  • Introduction
  • Rationale for Investigating Endophenotypes of Chronic Nicotine Exposure
  • Motivational Mechanisms
  • Acute Smoking or Abstinence Effects on Cognitive, Affective, and Physiological Function
  • Discussion and Recommendations for Future Research
  • Summary
  • Conclusions
  • References

Part 5 – Epidemiological and Methodological Considerations

• Chapter 10
  Epidemiological Analysis of Variation in Phenotypic Definitions: A Proof of Concept Using an Example of a Cessation Phenotype (214 kb)
  • Introduction
  • The Proposed Approach
  • Method
  • Summary
  • Conclusions
  • References


• Chapter 11
  Incorporating Social Context into Genetic Studies of Nicotine Dependence (214 kb)
  • Introduction
  • Why Incorporate the Social Context?
  • Behavioral Genetic Studies of Smoking That Incorporate Social Context
  • Proximal Measures of the Social Context
  • Future Directions
  • Summary
  • Conclusions
  • References


• Chapter 12
  Using Ontologies in Hierarchical Modeling of Genes and Exposure in Biological Pathways (2,048 kb)
  • Introduction
  • Methodological Issues
  • Background on Statistical Approaches
  • Methods
  • Example: Nicotine Metabolism
  • Discussion
  • Summary
  • Conclusions
  • Appendix 12 A. Estimation for the Hierarchical Model
  • Appendix 12 B. Model Selection Algorithm
  • References

Part 6 – Future Directions

• Chapter 13
  Future Directions (122 kb)
  • Introduction
  • Genetics and Nicotine Dependence: Implications for Basic and Clinical Research
  • Future Directions
  • References

Index (116 kb)