Statistical Methods in Genetic Epidemiology

ISBN-10: 019515939X
ISBN-13: 9780195159394
Edition: 2004
Authors: Duncan C. Thomas
List price: $78.00 Buy it from $39.80
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Description: This well-organized and clearly written text has a unique focus on methods of identifying the joint effects of genes and environment on disease patterns. It follows the natural sequence of research, taking readers through the study designs and  More...

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Book details

List price: $78.00
Copyright year: 2004
Publisher: Oxford University Press, Incorporated
Publication date: 1/29/2004
Binding: Hardcover
Pages: 464
Size: 6.00" wide x 10.00" long x 1.00" tall
Weight: 1.738
Language: English

This well-organized and clearly written text has a unique focus on methods of identifying the joint effects of genes and environment on disease patterns. It follows the natural sequence of research, taking readers through the study designs and statistical analysis techniques for determining whether a trait runs in families, testing hypotheses about whether a familial tendency is due to genetic or environmental factors or both, estimating the parameters of a genetic model, localizing and ultimately isolating the responsible genes, and finally characterizing their effects in the population. Examples from the literature on the genetic epidemiology of breast and colorectal cancer, among other diseases, illustrate this process. Although the book is oriented primarily towards graduate students in epidemiology, biostatistics and human genetics, it will also serve as a comprehensive reference work for researchers. Introductory chapters on molecular biology, Mendelian genetics, epidemiology, statistics, and population genetics will help make the book accessible to those coming from one of these fields without a background in the others. It strikes a good balance between epidemiologic study designs and statistical methods of data analysis.

Summary of Commonly Used Notation
Overview of Genetic Epidemiology
The Process of Genetic Epidemiology
Descriptive Epidemiology and Hypothesis Generation
Familial Aggregation
Segregation Analysis
Linkage Analysis
Fine Mapping and Cloning
Candidate Gene Association Studies
Characterizing the Effects of Cloned Genes
Conclusions
Basic Concepts of Molecular Genetics
Chromosomes
Cell Division
Cell Cycle
Mitosis
Meiosis
Genetic Recombination
Meiotic Recombination
Mitotic Recombination
DNA
Gene Expression
Transcription
RNA Processing
Translation
Post-Translational Modification
DNA Polymorphism
Conclusions
Principles of Mendelian Inheritance
Basic Concepts
Mendelian Inheritance at a Single Locus
Classical Autosomal Dominant Inheritance
Classical Autosomal Recessive Inheritance
Classical X-Linked Inheritance
Multiallelic Loci
Mendelian Inheritance at Two Loci
Conclusions
Basic Epidemiologic and Statistical Principles
Basic Probability Theory
Basic Epidemiologic Principles
Study Designs
Measures of Disease Frequency and Association
Interpretation of Epidemiologic Associations
Maximum Likelihood
Generalized Estimating Equations
Markov Chain Monte Carlo Methods
Randomization Procedures
Conclusions
Familial Aggregation
Genetic Relationships and Gene Identity
Formal Derivation of [phi] and [Delta]
Familial Correlations of Continuous Phenotypes
Familial Risk of Disease
The Concept of Familial Risk
Design Principles
Analytical Approaches
Other Designs
Randomization Tests of Familial Clustering
Twin Studies
Adoption Studies
Approaches to Dependent Data
Genetic Models
Regressive Models
Frailty Models
Generalized Estimating Equations
Conclusions
Segregation Analysis
Design Issues
Ascertainment of Families
Sequential Sampling
Classical Methods for Sibships
Ascertainment Correction
Likelihood Methods for Pedigree Analysis
General Model
Polygenic and Mixed Models
Penetrance Models
The Elston-Stewart Peeling Algorithm
Hypothesis Testing
Alternative Methods
Gibbs Sampling
Generalized Estimating Equations
Applications to Breast Cancer
Conclusions
Linkage Analysis
Recombination and Map Functions
Direct Counting Methods
Relative Pair Methods
Identity by State and by Descent
Affected Sib Pair Methods
Affected Relative Pair Methods
Sib Pair Methods for Quantitative Traits
Generalized Estimating Equation Methods
Lod Score Methods
Two-Point Linkage
Joint Segregation and Linkage Analysis and the Mod Score
Multipoint Linkage and Ordering Loci
Genome-Wide Scans
Genetic Heterogeneity
Gibbs Sampling Methods
Design Issues
Power and Sample Size
Selection Bias and Misspecification
Fine Mapping and Cloning of BRCA1
Conclusions
Principles of Population Genetics
Distribution of Genes at a Single Locus
Hardy-Weinberg Equilibrium in Large Populations
Genetic Drift in Finite Populations
Effects of Mutation and Selection
Distribution of Genes at Two Loci
Origins of Linkage Disequilibrium
Decay of Linkage Disequilibrium
Estimation of Linkage Disequilibrium
Evolution of Haplotypes
Ancestral Inference
Coalescent Trees
Ancestral Recombination Graphs
Conclusions
Testing Candidate Gene Associations
Distributions of Genes in Affected and Unaffected Individuals
Homogeneous Populations
Ethnically Stratified Populations
Families
Design Options for Association Studies
Cohort Study Designs
Case-Control Designs
Parental Controls and the Transmission/Disequilibrium Test
Family-Based Association Tests
Quantitative Traits
Conclusions
Linkage Disequilibrium Mapping
Recently Admixed Populations
Isolated Populations
Empiric Methods for Estimating the Location of a Disease Gene or Mutation
Haplotype Sharing Methods
Parametric Methods Based on the Coalescent
How Much Linkage Disequilibrium Is There in the Human Genome?
Haplotype Block Structure
Conclusions
Gene Characterization
Estimation of Genetic Risks
Cohort and Case-Control Designs Using Unrelated Subjects
Familial Cohort Study Designs
Multistage Sampling and Countermatching
Relative Efficiency of the Alternative Designs
Gene-Environment and Gene-Gene Interactions
Case-Control Designs
Case-Only Studies
Case-Parent Trios
Gene-Environment Interactions for Breast Cancer
Relative Efficiency of Alternative Designs for Interaction Effects
Estimation of Gene Frequencies and Carrier Probabilities
Searching for Additional Genes
Conclusions
Tying It All Together: the Genetic Epidemiology of Colorectal Cancer
History, Descriptive Epidemiology, and Familiality
Mechanistic Hypotheses
Models of Carcinogenesis
Cancer Genes
Genomic Instability
Familial Cancer Syndromes
Familial Adenomatous Polyposis
Hereditary Nonpolyposis Colorectal Cancer
Sporadic Cancers
Genetic Alterations in Colorectal Cancer
Pathways: Suppressor and Mutator
Metabolic Pathways
The Relationship Between Polyps and Colorectal Cancer
Discovery of Novel Colorectal Cancer Genes
Implications for Clinical Management
The Future
Genome-Wide Scans for Association and Interactions
Gene Expression Assays
DNA Methylation and Loss of Imprinting
Conclusions
Glossary
References
Index

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