Statistical Methods in Genetic Epidemiology.

Intro -- Contents -- SUMMARY OF COMMONLY USED NOTATION -- 1. 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 -- 2. 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 -- 3. 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 -- 4. 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 -- 5. FAMILIAL AGGREGATION -- Genetic Relationships and Gene Identity -- Formal Derivation of &amp -- #966 -- and &amp -- #916 -- -- 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 -- 6. 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 -- 7. 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 -- 8. 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 -- 9. 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 -- 10. 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 -- 11. 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 -- 12. 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 -- A -- B -- C -- D -- E.

F -- G -- H -- I -- K -- L -- M -- N -- O -- P -- Q -- R -- S -- T -- V -- W -- X -- REFERENCES -- INDEX -- A -- B -- C -- D -- E -- F -- G -- H -- I -- J -- K -- L -- M -- N -- O -- P -- Q -- R -- S -- T -- U -- V -- W -- X.

This balanced and well-integrated text gives a lucid overview of the entire process of genetic epidemiology, from familial aggregation through segregation, likage, and association studies. It is illustrated throughout with examples from the literature on cancer genetics. Statistical concepts are developed in depth, but with a focus on applications. Introductory chapters on molecular biology, Mendelian genetics, epidemiology, statistics, and population genetics are included. Oriented to graduate students in biostatistics, epidemiology, and human genetics, the book will also be a useful reference for researchers. It gives equal emphasis to study designs and data analysis.

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Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2024. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.