Genetic Epidemiology Methods and Applications

ISBN-10: 1780641818
ISBN-13: 9781780641812
Edition: 2013
List price: $39.95
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Description: Genetic epidemiology plays a key role in discovering genetic factors influencing health and disease, and in understanding how genes and environmental risk factors interact. There is growing interest in this field within public health, with the goal  More...

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Book details

List price: $39.95
Copyright year: 2013
Publisher: CABI
Publication date: 6/27/2013
Binding: Paperback
Pages: 216
Size: 7.44" wide x 9.69" long x 0.51" tall
Weight: 2.376
Language: English

Genetic epidemiology plays a key role in discovering genetic factors influencing health and disease, and in understanding how genes and environmental risk factors interact. There is growing interest in this field within public health, with the goal of translating the results into promoting health and preventing disease in both families and populations. This textbook provides graduate students with a working knowledge of genetic epidemiology research methods. Following an overview of the field, the book reviews key genetic concepts, provides an update on relevant genomic technology, including genome-wide chips and DNA sequencing, and describes methods for assessing the magnitude of genetic influences on diseases and risk factors. The book focuses on research study designs for discovering disease susceptibility genes, including family-based linkage analysis, candidate gene and genome-side association studies, assessing gene-environment interactions and epistasis, studies of Non-Mendelian inheritance, and statistical analyses of data from these studies. Specific applications of each research method are illustrated using a variety of diseases and risk factors relevant to public health, and useful web-based genetic analysis software, human reference panels, and repositories, that can greatly facilitate this work, are described.

M. A. Austin teaches at the University of Washington.

Contributors
Foreword
Acknowledgments
The Evolving Field of Genetic Epidemiology
Introduction
Assessing Genetic Influences on Disease, Human Genetics Concepts, and Genomic Technology
Family-based Study Designs: Linkage, Exome Sequencing and Case-Parent Trios
Genetic Association Studies of Common and Rare Variants, Large-scale Collaborations, and Population Stratification
Gene-Environment Interactions, Epistasis, and Non-Mendelian Genetics
Software and Data Resources
Ethical Issues and Translational Genetic Epidemiology
Conclusion
Assessing Genetic Influences on Diseases and Risk Factors
Introduction
Familial Aggregation Studies
Familial aggregation study designs
Heritability Analysis
Polygenic model
Estimating heritability using twins
Assumptions, biases, and misconceptions in heritability analysis
Conclusion: Heritability and the Polygenic Model in the Genomic Era
Genetic Concepts and Genomic Technology for Genetic Epidemiology
Introduction
Mendelian Inheritance and Complex Traits
Mendel's laws
Modes of inheritance for single genes
Online Mendelian Inheritance in Man (OMIM�)
Complex traits
Hardy-Weinberg Principle
Deviations from Hardy-Weinberg equilibrium
Genetic Code, Gene Structure, and Genetic Markers
Exons, introns, and untranslated regions
Single nucleotide polymorphisms (SNPs) and structural variations
Genetic Linkage and Linkage Disequilibrium
Genetic linkage and recombination
Linkage disequilibrium and haplotypes
Tag SNPs
SNP genotyping platforms
DNA Sequencing Technologies
Three generations of DNA sequencing
Exome sequencing
Study Designs for Common and Rare Genetic Variants
Conclusion
Family Studies in Genetic Epidemiology: From Linkage to Exome Sequencing
Linkage Analysis
Basics of LOD score linkage analysis
Non-parametric linkage analysis
Family-based Association Studies
Linkage and association in families
Case-parent trios and the transmission disequilibrium test (TDT)
Extensions of the TDT
Conclusion
Genetic Association Studies
Introduction to Genetic Association Studies
Study Designs for Candidate Gene Studies
Practical considerations for selecting candidate genes
Complexities of Interpreting Genetic Association Results
Direct, causal relationship
Indirect association due to linkage disequilibrium
False-positive associations
False-negative associations and power
Basics of Genome-wide Association Studies (GWAS)
GWAS case-control studies
Data analysis of GWAS
Large-scale Collaborations: The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
The CHARGE Consortium
CHARGE goals and organization
Genome-wide genotyping methods
Design of CHARGE analyses
Phenotype working groups
Analysis methods
Productivity
Collaborations with non-CHARGE studies and other consortia
Working-group model as innovation
A new era of consortia
CHARGE: past, present, and future
Facilitating large-scale collaborations
Case-Parent Trio Designs in GWAS
Heritability and Allelic Architecture of Complex Traits
Missing heritability in GWAS
Study Designs and Statistical Analysis of DNA Sequencing Data
Study designs for rare genetic variants
Methods for detecting association with rare variants
Conclusion
Population Stratification in Genetic Association Studies
General Concepts
Rationale for GWAS
Population stratification confounding
Detecting Population Stratification
Statistical Methods to Adjust for Global Population Stratification Confounding
Genomic control
Ethnicity adjustment
Principal components adjustment
Estimated ancestry adjustment
Estimated correlation methods
Statistical Methods to Adjust for Local Population Stratification Confounding
Mixing of populations and local population structure
Lactase persistence gene
Controlling for local ancestry
Conclusion
Gene-Environment Interactions and Epistasis
Why Study Interaction?
Models of Interaction
Statistical Interaction and the Problem of Measurement Scale
Statistical analysis of interaction for cohort and case-control studies
Multiplicative and additive measurement scales
Causal modeling applied to interaction
Case-only Study Design
Considerations for case-only studies
Pharmacogenomics
Gene-Environment-wide Interaction Studies (GEW1S)
Harmonization of environmental data
GEWIS data analysis approaches
Epistasis: Interactions Between Genes
Conclusion
Non-Mendelian Genetics
Introduction
Mitochondrial Genetics
De Novo Variation
Parental and Parent-of-origin Effects
DNA Methylation: An Epigenetic Mechanism Underlying Phenotypic Variation
Conclusion
Software and Data Resources for Genetic Epidemiology Studies
Introduction
Software for Genetic Data Analysis
R software
PLINK
Software for association testing in samples from structured populations
Individual ancestry estimation software
Relatedness estimation software for GWAS
Software for power calculations in genetic association studies
Genotype imputation software
An alphabetical list of genetic analysis software
Human Reference Panels and Resources
International HapMap Project (HapMap)
1000 Genomes Project
Human Generic Diversity Panel (HGDP)
Genome Variation Server
Genotype and Phenotype Repositories
Conclusion
Ethical Issues in Genetic Epidemiology
Introduction
Current Regulatory Environment
Trade-offs of Data De-identification
Informed Consent and Respect
Research Governance
Conclusion
Public Health and Clinical Applications of Genetic Epidemiology
Introduction
T1: From Discovery to Candidate Health Application
T2: From Health Application to Evidence-based Guidelines
T3: From Guidelines to Health Practice
T4: From Practice to Population Health Impact
Conclusion
Index

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