A Statistical Approach to Genetic Epidemiology: Concepts and Applications / Edition 1

A Statistical Approach to Genetic Epidemiology: Concepts and Applications / Edition 1

by Andreas Ziegler, Inke R. Konig
     
 

ISBN-10: 3527312528

ISBN-13: 9783527312528

Pub. Date: 03/31/2006

Publisher: Wiley

Covering the latest developments, this advanced textbook focuses on introducing the relevant statistical methods applied in this field. Written by the prize-winning scientist Andreas Ziegler, President of the German Region of the International Biometric Society, and Inke R. K?nig, who contributes more than five years of teaching experience, this is ideal for

Overview

Covering the latest developments, this advanced textbook focuses on introducing the relevant statistical methods applied in this field. Written by the prize-winning scientist Andreas Ziegler, President of the German Region of the International Biometric Society, and Inke R. K?nig, who contributes more than five years of teaching experience, this is ideal for epidemiologists, geneticists, statistics specialists, biomathematicians, graduate and undergraduate students.
After providing a concise introduction to genetic fundamentals, the authors explain both linkage analysis and association analysis in detail. This includes novel techniques such as haplotype tagging or linkage disequilibrium maps. The textbook features more than 100 problems and solutions.
With a foreword by Robert C. Elston, Director, Division of Genetic and Molecular Epidemiology at the Case Western Reserve University, Cleveland, Ohio.

Product Details

ISBN-13:
9783527312528
Publisher:
Wiley
Publication date:
03/31/2006
Edition description:
Older Edition
Pages:
361
Product dimensions:
7.09(w) x 9.63(h) x 0.93(d)

Table of Contents


Foreword     vii
Preface     ix
Acknowledgments     xi
Molecular Genetics     1
Genetic information     2
Location of genetic information     2
Interpretation of genetic information     5
Translation of genetic information     5
Transmission of genetic information     7
Variations in genetic information     10
Individual differences in genetic information     10
Detection of variations     11
Problems     15
Formal Genetics     17
Mendel and his laws     18
Segregation patterns     19
Autosomal dominant inheritance     20
Autosomal recessive inheritance     21
X-chromosomal dominant inheritance     22
X-chromosomal recessive inheritance     23
Y-chromosomal inheritance     24
Complications of Mendelian segregation     24
Variable penetrance and expression     25
Age-dependent penetrance     27
Imprinting     29
Phenotypic and genotypic heterogeneity     31
Complex diseases     32
Hardy-Weinberg law     34
Problems     39
Genetic Markers     43
Properties of genetic markers     43
Types of genetic markers     48
Short tandem repeats (STRs)     48
Single nucleotide polymorphisms (SNPs)     50
Problems     52
Data Quality     55
Pedigree errors     55
Genotyping errors in pedigrees     56
Frequency of genotyping errors     57
Reasons for genotyping errors     58
Mendel checks     59
Checks for double recombinants     61
Genotyping errors in population-based studies     63
Causes of deviations from Hardy-Weinberg equilibrium     63
Tests for deviation from Hardy-Weinberg equilibrium for SNPs     64
Tests for deviation from Hardy-Weinberg equilibrium for STRs     67
Tests for compatibility with Hardy-Weinberg for SNPs     69
Problems     72
Genetic Map Distances     75
Physical distance     75
Map distance     76
Distance     76
Specific map functions     77
Correspondence between physical distance and map distance     78
Multilocus feasibility     79
Radiation hybrid distance     80
Linkage disequilibrium distance     81
Problems     86
Model-based Linkage Analysis     89
Linkage analysis between two genetic markers     90
Linkage analysis in phase-known pedigrees     90
Linkage analysis in phase-unknown pedigrees     94
Linkage analysis in pedigrees with missing genotypes     95
Linkage analysis between a genetic marker and a disease     101
Linkage analysis between a genetic marker and a disease in phase-known pedigrees     101
Linkage analysis between a genetic marker and a disease in general cases     105
Gain in information by genotyping additional individuals; power calculations     110
Significance levels in linkage analysis     112
Problems     116
Model-free Linkage Analysis     121
The principle of similarity     122
Mathematical foundation of affected sib-pair analysis     124
Common tests for affected sib-pair analysis     125
The maximum LOD score and the triangle test     126
Score- and Wald-type one-degree-of-freedom tests     131
Affected sib-pair tests using alleles shared identical by state     136
Properties of affected sib-pair tests      137
Sample size and power calculations for affected sib-pair studies     139
Recurrence risk ratios     139
Relationship between recurrence risk ratios and IBD probabilities     142
Sample size and power calculations for the mean test using recurrence risk ratios     144
Extensions to multiple marker loci     146
Extension to large sibships     148
Extension to large pedigrees     149
Extensions of the affected sib-pair approach     150
Covariates in affected sib-pair analyses     151
Multiple disease loci in affected sib-pair analyses     151
Estimating the position of the disease locus in affected sib-pair analyses     151
Typing unaffected relatives in sib-pair analyses     152
Problems     153
Quantitative Traits     155
Quantitative versus qualitative traits     156
The Haseman-Elston method     157
The simple Falconer model     159
The expected squared phenotypic difference at the trait locus     161
The expected squared phenotypic difference at the marker locus     163
Extensions of the Haseman-Elston method     167
Double squared trait difference     167
Extension to large sibships      168
Haseman-Elston revisited and the new Haseman-Elston method     169
Power and sample size calculations     173
Further extensions of the Haseman-Elston method     176
Variance component models     177
The univariate variance component model     177
The multivariate variance component model     178
Random sib-pairs, extreme probands and extreme sib-pairs     181
Empirical determination of p-values     184
Problems     185
Fundamental Concepts of Association Analyses     187
Introduction to association     187
Principles of association     187
Study designs for association     189
Linkage disequilibrium     190
Measures for linkage disequilibrium     190
Extent of linkage disequilibrium     194
Problems     197
Association Analysis in Unrelated Individuals     199
Selection of cases and controls     200
Tests and estimates     200
Sample size calculation     205
Population stratification     208
Testing for population stratification     210
Structured association     211
Genomic control     212
Comparison of structured association and genomic control     213
Problems     213
Family-based Association Analysis     215
Haplotype relative risk     216
Transmission disequilibrium test (TDT)     217
Risk estimates for trio data     221
Sample size and power calculations for the TDT     223
Alternative test statistics     224
TDT for multiallelic markers     225
Test of single alleles     226
Global test statistics     226
TDT type tests for different family structures     228
TDT type tests for missing parental data     229
TDT type tests for sibship data     231
TDT type tests for extended pedigrees     236
Association analysis for quantitative traits     239
Problems     241
Haplotypes in Association Analyses     243
Reasons for studying haplotypes     244
Inference of haplotypes     245
Algorithms for haplotype assignment     245
Algorithms for estimating haplotype probabilities     247
Association tests using haplotypes     250
Haplotype blocks and tagging SNPs     252
Selection of markers by haplotypes      254
Selection of markers by linkage disequilibrium     257
Evaluation of marker selection approaches     259
Problems     261
Algorithms Used in Linkage Analyses     263
The Lander-Green algorithm     263
The inheritance vector at a single genetic marker     264
The inheritance distribution given all genetic markers     268
The Cardon-Fulker algorithm     274
Problems     276
Solutions     277
References     305
Index     329

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