Between the Lines of Genetic Code - 1st Edition - ISBN: 9780123970176, 9780123973023

Between the Lines of Genetic Code

1st Edition

Genetic Interactions in Understanding Disease and Complex Phenotypes

Editors: Leonid Padyukov
Hardcover ISBN: 9780123970176
eBook ISBN: 9780123973023
Imprint: Academic Press
Published Date: 23rd October 2013
Page Count: 232
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Between the Lines of Genetic Code lays out methodologies and tools for the measurement and evaluation of gene-gene and gene-environment studies and gives perspective on the future of this discipline. The book begins by defining terms for interaction studies, describing methodologies, and critically assessing the viability of current study designs and the possibilities for integrating designs. It then provides recent applications data with case studies in rheumatoid arthritis, multiple sclerosis, myositis and other complex human diseases. Last, it examines current studies and directions for future applications in patient care.

Recent multivariate studies show that gene-gene and gene-environment interactions can explain significant variances in inheritance that have previously been undetectable in univariate analysis. These links among genes and between genes and their environments during the development of diseases may serve as important hints for understanding pathogenic mechanisms and for developing new tools for prognosis, diagnosis, and treatment of various diseases.

Key Features

  • Systematically integrates methods of defining and detecting gene interactions to provide an overview of the field
  • Critically analyzes current methods and tools to aid researchers in integrating gene interaction studies
  • Includes examples of current biomedical applications and presents current research expected to shape clinical research in the near future


Research geneticists; molecular and cell biologists; biologists, bioinformaticians, and biostatisticians with interests in human disease

Table of Contents


List of Contributors


Interaction May be Confused with Many Different Things

Genetics in Human Diseases

Complex Human Diseases

Genome-Wide Association Studies as a Source of Information


Part One: Methodology

Chapter One. Terminology and Definitions for Interaction Studies

1.1 Introduction

1.2 Regression Models

1.3 The Linear Regression Model

1.4 Assumptions of Linear Regression Models

1.5 Estimation

1.6 Interaction on the Linear Scale

1.7 Logistic Regression Models

1.8 Other Nonlinear Regression Models

1.9 The Hazard Function and the Survival Function

1.10 Hazard Ratio

1.11 Assumptions

1.12 Interaction on the Logistic Scale

1.13 Estimating Multiplicative Interaction

1.14 Estimating Additive Interaction

1.15 Genetic Models

1.16 Summary


Chapter Two. Reducing Dimensionality in the Search for Gene–Gene Interactions

2.1 Introduction

2.2 Challenges in Searching for Gene–Gene Interactions

2.3 Data Mining Approaches for Gene–Gene Interactions

2.4 Example of a Data Mining Method: MDR

2.5 Strategies to Improve Power of Data Mining Methods

2.6 Computational Optimizations

2.7 Future of Gene–Gene Interaction Modeling

2.8 Conclusions


Chapter Three. Study Design for Interaction Analyses

3.1 Introduction

3.2 Study Base

3.3 Cohort Studies

3.4 Case-Control Studies

3.5 Systematic and Random Errors

3.6 Example of Gene–Environment Interaction

3.7 Summary


Chapter Four. High-Throughput Genetic Interaction Study

4.1 Introduction

4.2 Gene–Gene Interactions

4.3 Gene–Environment Interactions

4.4 Novel Statistic for Genome-Wide Interaction Analysis

4.5 Conclusions


Appendix 4.1 The Algorithm of the Forest-Based Haplotype Approach

Appendix 4.2 The FEPI-MB algorithm

Appendix 4.3 The bNEAT Algorithm

Appendix 4.4 The GEIRA Algorithm

Part 1. Conclusions


Part Two: Experimental Data

Chapter Five. Gene–Gene and Gene–Environment Interaction in Rheumatoid Arthritis

5.1 Introduction

5.2 Phenotypic Heterogeneity of Rheumatoid Arthritis: ACPAs

5.3 Genetic Risk Factors for Rheumatoid Arthritis

5.4 Nongenetic Factors in Risk for Rheumatoid Arthritis (Table 5.2)

5.5 Gene–Environment and Gene–Gene Interactions in Rheumatoid Arthritis (Table 5.3)



Chapter Six. Genetic and Environmental Risk Factors for Multiple Sclerosis—A Role for Interaction Analysis

6.1 Genetics of Multiple Sclerosis

6.2 Environmental Risk Factors for Multiple Sclerosis

6.3 Study of Interactions in Multiple Sclerosis

6.4 Gene–Gene Interactions

6.5 Gene–Environment Interactions

6.6 Conclusions: What Have We Learnt?


Chapter Seven. Gene–Gene and Gene–Environment Interactions in Defining Risk and Spectrum of Phenotypes in Idiopathic Inflammatory Myopathies

7.1 Clinical Introduction

7.2 Early HLA Results in Idiopathic Inflammatory Myopathies

7.3 HLA-Related Differences in PM/DM

7.4 The Association Between HLA Genes, Class II Haplotypes, and MSAs/MAAs

7.5 Contribution of HLA-DRB1 Gene Dose to Disease Phenotype and Severity in IBM

7.6 Remarkable Lessons from Statin-Induced Myositis

7.7 Cancer-Associated Myositis (CAM), HLA, and Anti-155/140 Autoantibodies

7.8 Relationship Between Smoking, HLA-DRB1*03, and Anti-Jo-1 in IIM

7.9 Possible Pathogenic Role of HLA and Autoantibodies


Part 2. Conclusions


Part Three: Future Avenues

Chapter Eight. Functional Studies of Gene–Gene Interaction of Autoimmune Diseases

8.1 Introduction

8.2 Attribution of Genetic Variation to Gene Function

8.3 Examples of Experimental Studies of Gene–Gene Interaction in Autoimmune Diseases

8.4 Conclusions


Chapter Nine. Genetic Vectors Approach in a Study of Fine Structure of Interaction Between Risk Haplotype of HTR2A and HLA-DRB1 Shared Epitope Alleles in Rheumatoid Arthritis

9.1 Introduction

9.2 Methods

9.3 Results

9.4 Discussion


Appendix Standard Correlations and Statistical Interaction

Chapter Ten. Network Biology Empowering Detection and Understanding of Interactions Between Genetic Factors in Development of Complex Phenotypes

10.1 Rise of Big Data, Computing, and Prediction

10.2 Using Genetic Variants as Independent Features is Not Sufficient for Realizing P4 Medicine

10.3 Network Biology—A Framework for Detecting and Interpreting Genetic Interactions

10.4 Inferring Genetic Interactions or Edges From Data is a Special Case of a Feature Selection Problem

10.5 Network Biology—A Framework for Detecting Genetic Interactions



Part 3. Conclusions



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© Academic Press 2014
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About the Editor

Leonid Padyukov


"Specialists in genetic epidemiology and human genetics, most at the Karolinski Institute in Stockholm, review the current status of the field and clarify the main definitions, recent findings, and future directions. They consider such topics as reducing dimensionality in the search for gene-gene interactions, high-throughput genetic interaction studies, gene-gene and gene-environment interaction in rheumatoid arthritis…", February 2014
"This book presents methodologies and tools for the measurement and evaluation of gene-gene and gene-environment studies of human diseases such as rheumatoid arthritis, multiple sclerosis, myositis, and other complex disorders…This is an excellent book on genetic interactions. Students, researchers, molecular biologists, and geneticists will find it quite useful." Rating: 3, January 24, 2014