Table Of ContentGenome-Wide Association Studies
From Polymorphism to Personalized Medicine
Over the last 20 years, Genome-Wide Association Studies (GWAS) have revealed a great
deal about the genetic basis of a wide range of complex diseases, and they will
undoubtedly continue to have a broad impact as we move to an era of personalized
medicine. This authoritative text, written by leaders and innovators from both acade-
mia and industry, covers the basic science as well as the clinical, biotechnological, and
pharmaceutical potential of these methods.
With special emphasis given to highlighting pharmaco-genomics and population
genomics studies using next-generation technology approaches, this is the first book
devoted to combining association studieswith single nucleotide polymorphisms, copy
number variants, haplotypes and expressed quantitative trait loci. A reliable guide for
newcomers to the field, aswell as for experienced scientists, this is a unique resource for
anyone interested in how the revolutionary power of genomics can be applied to solve
problems in complex disease.
KRISHNARAO APPASANI is the Founder and Chief Executive Officer of GeneExpression
Systems, a global conference-producing organization focusing on biomedical and
physical sciences. He is an award-winning scientist and also the editor of
Epigenomics: From Chromatin Biology to Therapeutics (2012), MicroRNAs: From Basic
Science to Disease Biology (2007), and RNA Interference: From Basic Science to Drug
Development (2005), all published by Cambridge University Press.
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Genome-Wide Association
Studies
FROM POLYMORPHISM TO PERSONALIZED MEDICINE
Edited by
Krishnarao Appasani
GeneExpression Systems, Inc.
Forewords by
Stephen W. Scherer
University of Toronto, Canada
and
Peter M. Visscher
University of Queensland, Australia
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First published 2016
Printed in the United States of America by Sheridan Books, Inc.
A catalogue record for this publication is available from the British Library
Library of Congress Cataloguing in Publication data
Genome-wide association studies : frompolymorphism to personalizedmedicine / edited by
Krishnarao Appasani ; forewords by Stephen W. Scherer and Peter M. Visscher.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-107-04276-6 (hardback)
I. Appasani, Krishnarao, 1959–, editor.
[DNLM: 1. Genome –Wide Association Study. 2. Genetic Testing. 3. Genomics. QU 550]
RB155
0
616 .042–dc23
2015017921
ISBN 978-1-107-04276-6 Hardback
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Dedicated to
My friend, Arthur Beck Pardee
Emeritus Professor
Harvard University Medical School, USA
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Contents
List of contributors page ix
Forewords by Stephen W. Scherer and Peter M. Visscher xix
Preface xxiii
List of abbreviations xxvi
Part I. Genome-wide association studies 1
1. Introduction to genome-wide association studies and personalized
medicine 3
Krishnarao Appasani and Raghu K. Appasani
2. GWAS: a milestone in the road from genotypes to phenotypes 12
Urko M. Marigorta, Juan Antonio Rodriguez and Arcadi Navarro
3. Introduction to statistical methods in genome-wide
association studies 26
Can Yang, Cong Li, Dongjun Chung, Mengjie Chen, Joel Gelernter
and Hongyu Zhao
4. GWAS replicability across time and space 53
Urko M. Marigorta, Juan Antonio Rodriguez and Arcadi Navarro
Part II. Genome-wide studies in disease biology 67
5. Genome-wide association studies of body mass index 69
Tuomas O. Kilpeläinen
6. Identification of myocardial infarction-susceptible genes
and their functional analyses 79
Kouichi Ozaki and Toshihiro Tanaka
7. Admixture mapping for disease gene discovery 89
Randall C. Johnson, Cheryl A. Winkler and Meredith Yeager
8. Genome-wide association analysis in schizophrenia 106
Sven Stringer, Dorien H. Nieman, René S. Kahn, and Eske M. Derks
9. Epigenome-wide association studies in neurodevelopmental
disorders 123
Takeo Kubota, Kunio Miyake and Takae Hirasawa
vii
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viii Contents
Part III. Single nucleotide polymorphisms, copy number variants,
haplotypes and eQTLs 137
10. Finding SNPs that affect microRNA regulation in disease-associated
genomic regions 139
Laurent F. Thomas and Pål Sætrom
11. From linkage to complex associations: the role of GABRA2 as a risk
factor for alcohol use 151
Sandra M. Villafuerte, Elisa M. Trucco and Margit Burmeister
12. Copy number variation in monozygous twins 168
Erwin Brosens, K.G. Snoek, D. Veenma, H. Eussen, D. Tibboel, and
A. de Klein
13. Haplotypes of CpG-related SNPs and associations with DNA
methylation patterns 193
Yiyi Ma, Caren E. Smith, Yu-Chi Lee, Laurence D. Parnell,
Chao-Qiang Lai and José M. Ordovás
14. eQTL mapping 208
Mengjie Chen, Can Yang, Cong Li and Hongyu Zhao
Part IV. Next-generation sequencing technology
and pharmaco-genomics 229
15. Next-generation sequencing for rare diseases 231
Elena Bosch and Ferran Casals
16. Next-generation sequencing for complex disorders 243
Ferran Casals and Elena Bosch
17. Chromosomal breakpoints in breast cancer co-localize with
differentially methylated regions 255
Man-Hung Eric Tang, Vinay Varadan, Sitharthan Kamalakaran,
Michael Q. Zhang, James Hicks and Nevenka Dimitrova
18. Signaling network analysis of genomic alterations predicts
breast cancer drug targets 269
Naif Zaman and Edwin Wang
19. Pharmacogenetic studies in pediatric acute myeloid leukemia 281
Neha S. Bhise, Lata Chauhan and Jatinder Kaur Lamba
20. Pharmaco-genomics of antiretroviral drugs 297
Chonlaphat Sukasem, Apichaya Puangpetch and Sadeep Medhasi
Part V. Population genetics and personalized medicine 313
21. Population stratification and its implications: lessons from
genome-wide studies 315
Sheikh Nizamuddin, Rakesh Tamang and Kumarasamy Thangaraj
22. How to solve genetic disease on a population scale 341
Barry Merriman
23. Economics of personalized medicine 366
Katherine Payne and Martin Eden
Index 383
The colour plates are to be found between pages 192 and 193
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Contributors
Krishnarao Appasani
GeneExpression Systems, Inc.
Waltham, Massachusetts, USA
Raghu Appasani
University of Massachusetts Medical School
Worcester, Massachusetts, USA &
MINDS Foundation USA & India
Boston, Massachusetts, USA
Neha S. Bhise
Department of Pharmacotherapy and Translational Research
Center for Pharmacogenomics
College of Pharmacy, University of Florida
Gainesville, FL, USA &
Department of Experimental and Clinical Research
University of Minnesota
St. Paul, Minnesota, USA
Elena Bosch
Institut de Biologia Evolutiva (UPF-CSIC)
Departament de Ciències Experimentals i de la Salut
Universitat Pompeu Fabra
Parc de Recerca Biomèdica de Barcelona
Barcelona, Catalonia, Spain
Erwin Brosens
PhD student Pediatric Surgery & Clinical Genetics
Erasmus MC–Sophia Children’s Hospital
GE Rotterdam, The Netherlands
ix
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x List of contributors
Margit Burmeister
Molecular & Behavioral Neuroscience Institute
University of Michigan
Ann Arbor, Michigan, USA
Ferran Casals
Genomics Core Facility
Departament de Ciències Experimentals i de la Salut
Universitat Pompeu Fabra
Barcelona, Catalonia, Spain
Lata Chauhan
Department of Pharmacotherapy and Translational Research
Center for Pharmacogenomics
College of Pharmacy
University of Florida
Gainesville, Florida, USA
Mengjie Chen
Department of Biostatistics
School of Public Health
Yale University
New Haven, Connecticut, USA &
Presently at Department of Biostatistics and Genetics
University of North Carolina Chapel Hill, NC, USA
Dongjun Chung
Department of Biostatistics
School of Public Health
Yale University
New Haven, Connecticut, USA
Eske M. Derks
Department of Psychiatry
Amsterdam Medical Center
University of Amsterdam
Amsterdam, The Netherlands
Nevenka Dimitrova
Philips Research
Briarcliff Manor, New York, USA
Martin Eden
Manchester Centre for Health Economics
The University of Manchester
Manchester, UK
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