Analysis of genetic association studies:
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| Format: | Book |
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| Language: | English |
| Published: |
New York, NY [u.a.]
Springer
2012
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| Series: | Statistics for biology and health
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis Klappentext |
| Physical Description: | XXII, 414 S. graph. Darst. |
| ISBN: | 9781461422440 |
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| 245 | 1 | 0 | |a Analysis of genetic association studies |c Gang Zheng ... |
| 264 | 1 | |a New York, NY [u.a.] |b Springer |c 2012 | |
| 300 | |a XXII, 414 S. |b graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
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| _version_ | 1804149093552881664 |
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| adam_text | Contents
Part I Background
1
Introduction to Probability Theory and Statistics
........... 3
1.1
Basic Probability Theory
...................... 4
1.1.1
Introduction
......................... 4
1.1.2
Marginal and Conditional Distributions
........... 5
1.1.3
Basic Distributions
...................... 6
1.1.4
Order Statistics
........................ 12
1.1.5
Convergence
......................... 14
1.2
Statistical Inference
......................... 15
1.2.1
Estimation and Confidence Intervals
............ 15
1.2.2
Testing Hypotheses
..................... 18
1.2.3
Likelihood-Based Test Statistics: Without a Nuisance
Parameter
.......................... 20
1.2.4
Likelihood-Based Test Statistics: With a Nuisance Parameter
21
1.2.5
Multiple Testing
....................... 22
1.3
The Delta Method
.......................... 24
1.4
The Newton-Raphson Method
.................... 25
1.5
The EM Algorithm
.......................... 25
1.6
Sample Size and Power
....................... 27
1.7
Asymptotic Relative Efficiency
................... 28
1.8
Bibliographical Comments
..................... 29
1.9
Problems
............................... 30
2
Introduction to Genetic Epidemiology
................. 33
2.1
Basic Genetic Terminology
..................... 34
2.2
Genetic Association Studies
..................... 36
2.2.1
Linkage Disequilibrium and Association Studies
...... 36
2.2.2
Population-Based Designs
.................. 38
2.2.3
Family-Based Designs
.................... 39
2.2.4
Other Designs
........................ 39
xiv Contents
2.3 Hardy-Weinberg
Principle
...................... 40
2.3.1
What Is Hardy-Weinberg Equilibrium?
........... 40
2.3.2
Testing Hardy-Weinberg Equilibrium Proportions
..... 43
2.3.3
Impact of Hardy-Weinberg Equilibrium or Disequilibrium
. 48
2.4
Population Substructure
....................... 48
2.4.1
Population Stratification
................... 49
2.4.2
Cryptic Relatedness
..................... 50
2.5
Odds Ratio and Relative Risk
.................... 51
2.5.1
Odds Ratios
......................... 51
2.5.2
Relative Risks
........................ 53
2.6
Logistic Regression for Case-Control Studies
............ 55
2.6.1
Prospective Case-Control Design
.............. 55
2.6.2
Retrospective Case-Control Design
............. 55
2.7
Bibliographical Comments
..................... 57
2.8
Problems
............................... 58
Part II Single-Marker Analysis for Case-Control Data
3
Single-Marker Analysis for Unmatched Case-Control Data
..... 61
3.1
Penetrance
and Genotype Relative Risks
.............. 62
3.2
Genetic Models
........................... 63
3.3
Genotype-Based Tests
........................ 65
3.3.1
Cochran-Armitage Trend Tests
............... 65
3.3.2
Trend Test Obtained from the Logistic Regression Model
. 67
3.3.3
Pearson s Chi-Squared Test
................. 69
3.3.4
Pearson s Test Obtained from the Logistic Regression Model
69
3.3.5
Other Likelihood-Based Tests
................ 70
3.4
Allele-Based Test
.......................... 71
3.4.1
Test Statistics
........................ 71
3.4.2
Comparison of the Allele-Based Test with the Trend Test
. 72
3.5
Exact Tests
.............................. 74
3.5.1
Exact Tests
.......................... 75
3.5.2
Permutation Approach
.................... 76
3.5.3
Parametric Bootstrap Approach
............... 77
3.6
Hardy-Weinberg Disequilibrium Trend Test
............. 78
3.7
Combining the HWDTT and the CATT
............... 79
3.8
Estimates of Odds Ratios
...................... 83
3.9
Simulating Case-Control Samples
.................. 84
3.9.1
Without Covariates
..................... 84
3.9.2
With Covariates
....................... 85
3.10
Adjusting out Covariates
....................... 86
3.11
Examples and Case Studies
..................... 87
3.11.1
Data from Genome-Wide Association Studies
....... 87
3.11.2
Association Tests
...................... 87
3.11.3
Estimates of Odds Ratios
.................. 88
3.12
Bibliographical Comments
..................... 90
3.13
Problems
............................... 92
Contents
Single-Marker Analysis for Matched Case-Control Data
....... 95
4.1
Notation and Models
......................... 96
4.2
Conditional Likelihoods for Matched Case-Control Data
...... 99
4.3
Matched Trend Tests
......................... 99
4.3.1 1 :
m
Matching
........................ 100
4.3.2
A Variable Number of Controls and a Case Are Matched
. . 102
4.4
Matching Disequilibrium Tests
................... 103
4.4.1
A Variable Number of Controls and a Case Are Matched
. . 103
4.4.2 1
:m Matching
........................ 104
4.5
A Model-Free Test
.......................... 105
4.5.1
A Variable Number of Controls and a Case Are Matched
. . 105
4.5.2 1 :
m
Matching
........................ 106
4.6
Multiple Cases and Multiple Controls Are Matched
........ 109
4.7
Simulating Matched Case-Control Data
............... 110
4.8
Performance of the Three Test Statistics
.............. 112
4.9
Estimates of Odds Ratios and Relative Risks
............ 113
4.9.1
Conditional Odds Ratios
................... 114
4.9.2
Relative Risks
........................ 116
4.10
Bibliographical Comments
..................... 117
4.11
Problems
............................... 117
Bayes
Factors for Case-Control Association Studies
.......... 121
5.1
Introduction
............................. 122
5.2
Bayes
Factor
............................. 123
5.2.1
Definition
.......................... 123
5.2.2
Interpreting
Bayes
Factors
.................. 123
5.2.3
Approximations of
Bayes
Factors
.............. 124
5.3
Bayes
Factor for Genetic Association Studies
............ 127
5.3.1
Laplace Approximation
................... 128
5.3.2
An Example
......................... 130
5.3.3
Coding the Genetic Effect
.................. 132
5.4
Approximate
Bayes
Factor for Genetic Association Studies I
... 132
5.4.1
NoCovariates
........................ 133
5.4.2
With Covariates
....................... 134
5.4.3
An Alternative Derivation
.................. 135
5.4.4
Coding the Genetic Effect
.................. 135
5.4.5
An Example
......................... 136
5.5
Approximate
Bayes
Factor for Genetic Association Studies II
... 136
5.5.1
With Covariates
....................... 137
5.5.2
NoCovariates
........................ 139
5.5.3
An Example
......................... 140
5.6
Prior Specification
.......................... 141
5.6.1
Prior for Using a Single Parameter
............. 141
5.7
Simulation Studies Using Approximate
Bayes
Factors
....... 143
5.8
Bibliographical Comments
..................... 145
5.9
Problems
............................... 147
Contents
Robust
Procedures
............................ 151
6.1 Robust
Hypothesis
Testing
...................... 152
6.1.1
Discrete
Numbers of Alternative
Hypotheses
........ 152
6.1.2
Alternative Hypothesis Indexed by an Interval
....... 153
6.1.3 Maximin
Efficiency
..................... 153
6.2 Maximin
Efficiency Robust Test
................... 156
6.2.1
The
MERT
as a Robust Test
................. 156
6.2.2
The
MERT
Versus a Single Trend Test for Genetic
Association
......................... 159
6.3
Max Statistics
............................ 161
6.3.1
MAX3
............................ 162
6.3.2
Monte-Carlo Approaches for MAX3
............ 164
6.3.3
Asymptotic Distribution of MAX3
............. 166
6.3.4
Approximation of the Tail of the Distribution of MAX3:
The Rhombus Formula
................... 169
6.3.5
MAX
............................. 170
6.3.6
Comparing MAX2, MAX3 and MAX
............ 170
6.3.7
Relationship Among MAX, Trend Test and Pearson s Test
. 171
6.3.8
Examples
........................... 173
6.4
MIN2
................................. 176
6.4.1
Joint Distribution and P-Value
................ 176
6.4.2
MIN2 Versus the P-Value of MIN2
............. 177
6.4.3
Examples
........................... 177
6.5
The Constrained Likelihood Ratio Test
............... 178
6.5.1
Restricted Maximum Likelihood Estimates of
Penetrances
. 179
6.5.2
Examples
........................... 179
6.6
Genetic Model Selection
....................... 180
6.6.1
Hardy-Weinberg Disequilibrium and Genetic Models
... 181
6.6.2
Performance of the Genetic Model Selection
........ 182
6.6.3
Testing Association After the Genetic Model Selection
. . . 184
6.6.4
Examples
........................... 187
6.6.5
Choice of Thresholds for the Genetic Model Selection
... 188
6.6.6
Simulating the Null Distribution
.............. 190
6.7
Genetic Model Exclusion
...................... 191
6.7.1
Reducing the Genetic Model Space
............. 191
6.7.2
The MERT-Based Genetic Model Exclusion Test
...... 192
6.7.3
Examples
........................... 195
6.7.4
The MAX-Based Genetic Model Exclusion Test
...... 196
6.8
Simulation Studies with Robust Tests
................ 196
6.8.1
Critical Values and Type I Errors
.............. 196
6.8.2
Empirical Power
....................... 198
6.8.3
Discussion
.......................... 199
6.9
MAX3 for Matched Pair Designs
.................. 200
6.10
Bibliographical Comments
..................... 202
6.11
Problems
............................... 204
Contents xvü
Part III Multi-marker Analyses for Case-Control Data
7
Haplotype Analysis for Case-Control Data
...............209
7.1
Haplotype Inference
.........................210
7.1.1
Phase and Phase Ambiguity
................. 210
7.1.2
Haplotype Reconstruction
.................. 211
7.1.3
Estimating Haplotype Frequencies
............. 212
7.2
Linkage Disequilibrium
....................... 215
7.2.1
Linkage Disequilibrium Coefficients
............ 215
7.2.2
Testing for Linkage Equilibrium
.............. 216
7.2.3
Haplotype Block and Haplotype-Tagging SNPs
...... 217
7.3
Haplotype-Based Population Association Analysis
......... 220
7.3.1
Likelihood Ratio Test
.................... 220
7.3.2
Regression Method
..................... 221
7.3.3
Haplotype Similarity
..................... 224
7.4
Linkage Disequilibrium Contrast Tests
............... 225
7.4.1
Composite LD Measure
................... 225
7.4.2
Contrasting LD Measures
.................. 228
7.5
Examples
............................... 229
7.6
Bibliographical Comments
..................... 229
7.7
Problems
............................... 232
8
Gene-Gene Interactions
.........................235
8.1
Two-Locus Association Analysis with Interactions
.........236
8.1.1
Saturated Logistic Regression Model
............236
8.1.2
Incorporating Two-Locus Genetic Models
.........238
8.2
Association Analysis with Higher-Order Interactions
........239
8.2.1
Multifactor Dimensionality Reduction
...........240
8.2.2
Logic Regression
......................242
8.3
Test for Two-Locus Interactions
...................243
8.3.1
A Representation of Two-Locus Interaction Effects
.... 246
8.3.2
Contrasting Log-Odds Ratios
................ 246
8.3.3
Relationship with the Log-Linear Model
.......... 248
8.3.4
Contrasting LD Measures
.................. 248
8.3.5
Test for Second-Order Interactions for Multiple Loci
. ... 251
8.3.6
Representation of Higher-Order Interactions
........ 251
8.4
Bibliographical Comments
..................... 253
8.5
Problems
............................... 255
Part IV Topics Related to Analysis of Case-Control Association
9
Population Structure
...........................259
9.1
Population Structure
.........................260
9.2
Impact of Population Stratification
.................262
9.2.1
A Model for Population Stratification
............262
9.2.2
Impact on Trend Tests
....................265
9.3
Correcting for Population Stratification
...............266
xviii Contents
9.3.1 Genomic
Control
......................266
9.3.2
Structural
Association
....................269
9.3.3
Principal Components and Clustering
............271
9.3.4
Multidimensional Scaling Plots
...............278
9.4
Selection of Marker Loci
......................279
9.5
Simulating Data in the Presence of Population Stratification
.... 280
9.6
Comparison of Methods
.......................281
9.7
Bibliographical Comments
.....................283
9.8
Problems
...............................285
10
Gene-Environment Interactions
.....................287
10.1
Introduction
.............................287
10.2
Gene-Environment Interactions and Inference
...........288
10.2.1
A
2
χ
2
χ
2
Table
...................... 288
10.2.2
An Example
......................... 292
10.2.3
More General
G
and
E
................... 294
10.2.4
Gene-Environment Independence
.............. 299
10.3
Test Statistics for Gene-Environment Interaction
.......... 301
10.3.1
Likelihood Ratio Test
....................301
10.3.2
Score Test
..........................302
10.3.3 Wald
Test
..........................303
10.3.4
Examples
...........................304
10.4
Bibliographical Comments
.....................306
10.5
Problems
...............................307
11
Power and Sample Size Calculations
..................309
11.1
Single Marker Analysis Using Trend Tests
.............310
11.1.1
Power and Sample Size Formulas
.............. 310
11.1.2
Perfect Linkage Disequilibrium
............... 312
11.1.3
Imperfect Linkage Disequilibrium
............. 313
11.2
Pearson s Chi-Squared Test
..................... 316
11.2.1
Example
........................... 318
11.2.2
Asymptotic Power of Pearson s Chi-Squared Test and the
TrendTest
.......................... 318
11.3
Using Odds Ratios
.......................... 319
11.4
Using a Power Program
....................... 320
11.4.1
Specifications
........................320
11.4.2
Examples
...........................321
11.4.3
Limitations
..........................324
11.5
Testing Interactions
.........................324
11.5.1
Score Statistic for an Interaction
...............324
11.5.2
Gene-Environment Interactions
...............326
11.5.3
Gene-Gene Interactions
...................330
11.6
Bibliographical Comments
.....................331
11.7
Problems
...............................332
Contents xix
Part V Introduction to Genome-Wide Association Studies
12
Genome-Wide Association Studies
................... 337
12.1
Introduction
............................. 337
12.2
Quality Control
........................... 338
12.3
Analysis of GWAS
.......................... 342
12.3.1
Genome-Wide Scans and Ranking
............. 342
12.3.2
Haplotype Analysis and Interactions
............ 346
12.4
Replication and Follow-Up
..................... 347
12.5
Bibliographical Comments
..................... 348
12.6
Problems
............................... 349
Part VI Introduction to Family-Based Association Studies
13
Analysis of Family Data
......................... 353
13.1
Model-Based Methods for Linkage Analysis
............ 354
13.2
Model-Free Methods for Linkage Analysis
............. 357
13.2.1
Estimating Marker Identity by Descent
........... 357
13.2.2
Interval Mapping
....................... 358
13.2.3
The Original Haseman-Elston (HE) Regression for a
Quantitative Trait
...................... 360
13.2.4
The New HE Regression
................... 360
13.2.5
Maximum Likelihood Variance Component Model
..... 361
13.2.6
Qualitative Traits
...................... 364
13.3
Transmission/Disequilibrium Test
.................. 366
13.4
Robust Methods
........................... 372
13.4.1
Linkage Analysis Using Affected Sibpairs
......... 372
13.4.2
Association Analysis Using Trios
.............. 374
13.5
Family-Based Methods for Linkage and Association Analysis:
FBAT
................................. 376
13.5.1
A General FBAT
....................... 376
13.5.2
Application to Parent-Offspring Trios
............ 377
13.5.3
A General Pedigree
..................... 378
13.5.4
FBAT Website and Software
................. 383
13.6
Bibliographical Comments
..................... 384
13.7
Problems
............................... 386
References
................................... 389
Index
...................................... 405
Statistics for Biology and Health
Gang Zheng
·
Yaning Vang
·
Xiaofeng
Zítu
■
Robert
C. Elston
Analysis of Genetic Association Studies
Analysis of Genetic Association Studies is both a graduate level textbook in statistical
genetics and genetic epidemiology, and a reference book for the analysis of genetic as¬
sociation studies. Students, researchers, and professionals will find the topics introduced
in Analysis of Genetic Association Studies particularly relevant. The book is applicable
to the study of statistics, biostatistics, genetics and genetic epidemiology.
In addition to providing derivations, the book uses real examples and simulations to
illustrate step-by-step applications. Introductory chapters on probability and genetic
epidemiology terminology provide the reader with necessary background knowledge.
The organization of this work allows for both casual reference and close study.
|
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| dewey-ones | 616 - Diseases |
| dewey-raw | 616.0420727 |
| dewey-search | 616.0420727 |
| dewey-sort | 3616.0420727 |
| dewey-tens | 610 - Medicine and health |
| discipline | Biologie Medizin |
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| id | DE-604.BV040129422 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T00:17:33Z |
| institution | BVB |
| isbn | 9781461422440 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-024986624 |
| oclc_num | 780331128 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR DE-19 DE-BY-UBM |
| owner_facet | DE-355 DE-BY-UBR DE-19 DE-BY-UBM |
| physical | XXII, 414 S. graph. Darst. |
| publishDate | 2012 |
| publishDateSearch | 2012 |
| publishDateSort | 2012 |
| publisher | Springer |
| record_format | marc |
| series2 | Statistics for biology and health |
| spelling | Analysis of genetic association studies Gang Zheng ... New York, NY [u.a.] Springer 2012 XXII, 414 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier Statistics for biology and health Statistische Analyse (DE-588)4116599-8 gnd rswk-swf Genetik (DE-588)4071711-2 gnd rswk-swf Genetik (DE-588)4071711-2 s Statistische Analyse (DE-588)4116599-8 s b DE-604 Zheng, Gang Sonstige oth Erscheint auch als Online-Ausgabe 978-1-4614-2245-7 Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=024986624&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=024986624&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
| spellingShingle | Analysis of genetic association studies Statistische Analyse (DE-588)4116599-8 gnd Genetik (DE-588)4071711-2 gnd |
| subject_GND | (DE-588)4116599-8 (DE-588)4071711-2 |
| title | Analysis of genetic association studies |
| title_auth | Analysis of genetic association studies |
| title_exact_search | Analysis of genetic association studies |
| title_full | Analysis of genetic association studies Gang Zheng ... |
| title_fullStr | Analysis of genetic association studies Gang Zheng ... |
| title_full_unstemmed | Analysis of genetic association studies Gang Zheng ... |
| title_short | Analysis of genetic association studies |
| title_sort | analysis of genetic association studies |
| topic | Statistische Analyse (DE-588)4116599-8 gnd Genetik (DE-588)4071711-2 gnd |
| topic_facet | Statistische Analyse Genetik |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=024986624&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=024986624&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT zhenggang analysisofgeneticassociationstudies |