human genome epidemiology 2nd edition building the evidence for using genetic information to improve health and prevent disease jan 2010

Human Genome
Epidemiology
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HUMAN GENOME
EPIDEMIOLOGY
Second Edition
Building the Evidence for
Using Genetic Information to
Improve Health and Prevent
Disease
Edited by
MUIN J. KHOURY
SARA R. BEDROSIAN
MARTA GWINN
JULIAN P. T. HIGGINS
JOHN P. A. IOANNIDIS
JULIAN LITTLE
1
2010
3
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Library of Congress Cataloging-in-Publication Data
Human genome epidemiology : building the evidence for using genetic information to improve health and prevent
disease / edited by Muin J. Khoury [et al.]. — 2nd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-19-539844-1
1. Genetic disorders—Epidemiology. 2. Medical genetics—Methodology. 3. Genomics. I. Khoury, Muin J.
[DNLM: 1. Genetics, Medical—methods. 2. Genetic Diseases, Inborn—epidemiology. 3. Genetic
Predisposition to Disease—epidemiology. 4. Genetic Screening. 5. Genome, Human. 6. Genomics.
QZ 50 H91674 2010]
RB155.5.H86 2010
616’.042—dc22
2009018899
9 8 7 6 5 4 3 2 1

Printed in the United States of America
on acid-free paper
v
In the  rst edition of Human Genome Epidemiology published in 2004, we discussed
how the epidemiologic approach provides an important scienti c foundation for
studying the continuum from gene discovery to the development, applications, and
evaluation of human genome information in improving health and preventing dis-
ease. Since 2004, advances in human genomics have continued to occur at a breath-
taking pace. Although the concept of personalized healthcare and disease prevention
often promised by enthusiastic scientists and the media is yet to be ful lled, we
are now seeing progress and rapid accumulation of data in many “omics” related
research  elds. New methods to measure genome variation on an unprecedented
large scale have propelled a new generation of genome-wide association studies.
Evaluation of rare variants and full sequencing at large-scale are rapidly becoming
a reality. Also, we have seen the emergence of population-based biobanks in many
countries with the objectives of quantifying longitudinally the joint in uences of
genetic and environmental factors on the occurrence of common diseases.
With all these ongoing developments, we have invited many authors who are lead-
ers in the  eld to produce the second edition of Human Genome Epidemiology. Our
aim is to inform readers of new developments in the genomics  eld and how epide-
miologic methods are being used to make sense of this information. We do realize
that the material presented in this book will be outdated even before it is published.
However, the methodologic challenges and possible solutions to them will remain
with us for quite some time. There is very little material remaining from the  rst
edition of Human Genome Epidemiology.
This new edition is divided into  ve parts. In Part I, we revisit the fundamentals
of human genome epidemiology. We  rst give an overview of the development and
progress in applications of genomic technologies with a focus on genomic sequence
variation (Chapter 2). We then give an overview of the multidisciplinary  eld of
public health genomics that includes a fundamental role of epidemiologic methods

and approaches (Chapter 3). We also present a brief overview of evolving methods
for tracking and compiling information on genetic factors in disease (Chapter 4).
In Part II, we discuss methodologic developments in collection, analysis, and syn-
thesis of data from human genome epidemiologic studies. We discuss the emergence
of biobanks around the world (Chapter 5), the evolution of case-control studies
and cohort studies in the era of GWAS (Chapter 6), and the emerging role of con-
sortia and networks (Chapter 7). Next, we discuss methodologic analytic issues in
GWAS (Chapter 8) and the analytic challenges of gene-gene and gene-environment
interaction (Chapter 9). We then address issues of reporting of genetic associations
Preface
vi

(Chapter 10), evolving methods for integrating the evidence (Chapter 11) as well as
assessment of cumulative evidence and  eld synopses (Chapter 12).
In Part III, we provide several case studies that attempt to present an evolving
knowledge base of the cumulative evidence on genetic variation in a variety of
human diseases. As the information undoubtedly will change (even before the publi-
cation of the book), we stress here the importance of strong methodologic foundation
for analysis and synthesis of information from various studies. The diseases shown
in this section include three cancers: colorectal cancer (Chapter 13), childhood leu-
kemia (Chapter 14), and bladder cancer (Chapter 15). We also present data from
type 2 diabetes (Chapter 16), osteoporosis (Chapter 17), preterm birth (Chapter 18),
coronary heart disease (Chapter 19), and schizophrenia (Chapter 20). Collectively,
these chapters cover an impressive array of common complex human diseases and
provide an epidemiologic approach to rapidly emerging data on gene-disease and
gene-environment interactions.
In Part IV, we discuss methodologic issues surrounding speci c applications of
human genomic information for medicine and public health. We start in Chapter 21
with a review of the concept of Mendelian Randomization, an approach that allows
us to assess the role of environmental factors and other biomarkers in the occur-

rence of human diseases using data on the association of genetic variation and dis-
ease endpoints. In Chapter 22, we discuss how clinical epidemiologic concepts and
methods can be used to assess whether or not one or more genetic variants (e.g.,
genome pro les) can be used to predict risk for human diseases. Chapter 23 presents
a major milestone for public health genomics, namely the publication of methods
of systematic review and assessment of the clinical validity and utility of genomic
applications in clinical practice. This chapter is a reprint of the published paper from
the independent multidisciplinary panel, the EGAPP working group, supported by
CDC and many partners. Chapter 24 brie y summarizes how reviews of the evi-
dence on validity and utility of genomic information can be done systematically
and rapidly, even in the face of incomplete information. Chapter 25 focuses on the
crucial role of the behavioral and social sciences in assessing the impact and value
of epidemiologic information on gene-disease associations. Chapter 26 addresses
issues in evaluating developments in newborn screening. Chapter 27 provides an
epidemiologic framework for the evaluation of pharmacogenomic applications in
clinical and public health practice. Chapter 28 presents an overview of the relevance
and impact of epigenomics in clinical practice and disease prevention. Finally, chap-
ter 29 presents an epidemiologic framework for evaluating family health history as a
tool for disease prevention and health promotion. Even in this genomics era, family
history remains a strong foundation, not only for identifying single gene disorders,
but also for stratifying individuals and populations by different levels of disease risk
and implementing personalized interventions.
Finally, in Part V of the book, we present a few case studies of the application
of epidemiologic methods of assessment of clinical validity and utility for several
disease examples. These include two pharmacogenomic testing examples—initial
vii
Preface
treatment of depression with SSRIs (Chapter 30) and warfarin therapy (Chapter 31).
We also present information on population screening for hereditary hemochroma-
tosis (Chapter 32), a genetic disorder with incomplete penetrance that has attracted

some attention over the past decade as a possible example of population screening
in the genomics era.
The second edition of Human Genome Epidemiology is primarily targeted to
basic, clinical, and population scientists involved in studying genetic factors in com-
mon diseases. In addition, the book focuses on practical applications of human
genome variation in clinical practice and disease prevention. We hope that students,
clinicians, public health professionals, and policy makers will  nd the book useful
in learning about evolving epidemiologic methods for approaching the discovery
and the use of genetic information in medicine and public health in the twenty- rst
century.
Atlanta MJK, SB, MG
Cambridge JH
Ioannina JI
Ottawa JL
2009
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ix
We are grateful to the following individuals for reviewing drafts of selected book
chapters:
Louise Acheson
Betsy Anagnostelis
Melissa Austin
Wylie Burke
Melinda Clyne
Rajvir Dahiya
W. David Dotson
Michael P. Douglas
Nicole Dowling
Jennifer L. Flome
Sara Giordano

Ridgely Fisk Green
Scott Grosse
Daurice A. Grossniklaus
Idris Guessous
Jennifer Harris
Steve Hawken
Terri Jackson
Candice Y. Johnson
Fontini Kavvoura
Katherine Kolor
Ruth Loos
Denise Lowe
Stephanie Melillo
Melanie Myers
Renée M. Ned
Nikolaos Patsopoulos
Paul Pharoah
Margaret Piper
Beth Potter
Jessica L. Rowell
Simon Sanderson
Linda Sharp
Camilla Stoltenberg
Acknowledgments
x

John Thompson
Rodolfo Valdez
Jan Vandenbroucke
David Veenstra

Bridget Wilcken
Lauren E. Williams
Quanhe Yang
Ajay Yesupriya
Wei Yu
xi
Contributors xv
PART I Fundamentals of Human Genome
Epidemiology Revisited
1. Human Genome Epidemiology: The Road Map Revisited 3
Muin J. Khoury, Sara R. Bedrosian, Marta Gwinn,
Julian Little, Julian P. T. Higgins, and John P. A. Ioannidis
2. Principles of Analysis of Germline Genetics 13
Jesus Gonzalez-Bosquet and Stephen J. Chanock
3. The Public Health Genomics Enterprise 36
Philippa Brice and Ron Zimmern
4. Navigating the Evolving Knowledge of Human Genetic
Variation in Health and Disease 63
Marta Gwinn and Wei Yu
PART II Methods and Approaches for Data
Collection, Analysis, and Integration
5. The Global Emergence of Epidemiological Biobanks: Opportunities
and Challenges 77
Paul R. Burton, Isabel Fortier, and Bartha M. Knoppers
6. Case-Control and Cohort Studies in the Age of Genome-wide
Associations 100
Teri Manolio
7. The Emergence of Networks in Human Genome
Epidemiology: Challenges and Opportunities 120
Daniela Seminara, Muin J. Khoury, Thomas R. O’Brien,

Teri Manolio, Marta Gwinn, Julian Little, Julian P. T. Higgins,
Jonine L. Bernstein, Paolo Boffetta, Melissa L. Bondy,
Molly S. Bray, Paul E. Brenchley, Patricia A. Bufer,
Juan Pablo Casas, Anand P. Chokkalingam, John Danesh,
Contents
xii

George Davey Smith, Siobhan M. Dolan, Ross Duncan,
Nelleke A. Gruis, Mia Hashibe, David J. Hunter, Marjo-Riitta Jarvelin,
Beatrice Malmer, Demetrius M. Maraganore, Julia A. Newton-Bishop,
Elio Riboli, Georgia Salanti, Emanuela Taioli, Nic Timpson,
André G. Uitterlinden, Paolo Vineis, Nick Wareham, Deborah M. Winn,
Ron Zimmern, and John P. A. Ioannidis
8. Design and Analysis Issues in Genome-wide Association
Studies 136
Duncan C. Thomas
9. The Challenge of Assessing Complex Gene–Environment
and Gene–Gene Interactions 165
Peter Kraft and David J. Hunter
10. STrengthening the REporting of Genetic Association Studies
(STREGA)—an Extension of the STROBE Statement 188
Julian Little, Julian P. T. Higgins, John P. A. Ioannidis,
David Moher, France Gagnon, Erik von Elm, Muin J. Khoury,
Barbara Cohen, George Davey Smith, Jeremy Grimshaw,
Paul Scheet, Marta Gwinn, Robin E. Williamson, Guang Yong Zou,
Kimberley Hutchings, Candice Y. Johnson, Valerie Tait,
Miriam Wiens, Jean Golding, Cornelia M. van Duijn,
John McLaughlin, Andrew Paterson, George Wells, Isabel Fortier,
Matthew Freedman, Maja Zecevic, Richard A. King,
Claire Infante-Rivard, Alexandre Stewart, and Nick Birkett

11. Integration of the Evidence on Gene-Disease Associations:
Methods of HuGE Reviews 215
Julian P. T. Higgins and Julian Little
12. Genome-wide Association Studies, Field Synopses, and the
Development of the Knowledge Base on Genetic Variation
and Human Diseases 227
Muin J. Khoury, Lars Bertram, Paolo Boffetta, Adam S. Butterworth,
Stephen J. Chanock, Siobhan M. Dolan, Isabel Fortier,
Montserrat Garcia-Closas, Marta Gwinn, Julian P. T. Higgins,
A. Cecile J. W. Janssens, James M. Ostell, Ryan P. Owen,
Roberta A. Pagon, Timothy R. Rebbeck, Nathaniel Rothman,
Jonine L. Bernstein

, Paul R. Burton, Harry Campbell,
Anand P. Chokkalingam, Helena Furberg, Julian Little,
Thomas R. O’Brien, Daniela Seminara, Paolo Vineis,
Deborah M. Winn, Wei Yu, and John P. A. Ioannidis
xiii
Contents
PART III Case Studies: Cumulative Assessment of the
Role of Human Genome Variation in Speci c Diseases
13. Colorectal Cancer 249
Harry Campbell, Steven Hawken, Evropi Theodoratou, Alex Demarsh,
Kimberley Hutchings, Candice Y. Johnson, Lindsey Masson, Linda Sharp,
Valerie Tait, and Julian Little
14. Childhood Leukemias 278
Anand P. Chokkalingam and Patricia A. Buf er
15. Bladder Cancer 299
Jonine D. Figueroa, Montserrat Garcia-Closas,
and Nathaniel Rothman

16. Type 2 Diabetes 326
Eleftheria Zeggini and Mark I. McCarthy
17. Osteoporosis 337
André G. Uitterlinden, Joyce B. J. van Meurs,
and Fernando Rivadeneira
18. Preterm Birth 357
Siobhan M. Dolan
19. Coronary Heart Disease 369
Adam S. Butterworth, Julian P. T. Higgins,
Nadeem Sarwar, and John Danesh
20. Schizophrenia 390
Lars Bertram
PART IV Applications of Epidemiologic Methods
for Using Genetic Information in Medicine and
Public Health
21. Mendelian Randomization: The Contribution of Genetic Epidemiology
to Elucidating Environmentally Modi able Causes of Disease 407
George Davey Smith and Shah Ebrahim
22. Evaluation of Predictive Genetic Tests for Common Diseases:
Bridging Epidemiological, Clinical, and Public Health Measures 445
A. Cecile J. W. Janssens, Marta Gwinn, and Muin J. Khoury
xiv

23. The Evaluation of Genomic Applications in
Practice and Prevention (EGAPP) Initiative:
Methods of the EGAPP Working Group 458
Steven M. Teutsch, Linda A. Bradley, Glenn E. Palomaki,
James E. Haddow, Margaret Piper, Ned Calonge, W. David Dotson,
Michael P. Douglas, and Alfred O. Berg
24. Rapid, Evidence-based Reviews of Genetic Tests 482

James M. Gudgeon, Glenn E. Palomaki, and Marc S. Williams
25. Role of Social and Behavioral Research in Assessing the Utility of
Genetic Information 497
Saskia C. Sanderson, Christopher H. Wade, and Colleen M. McBride
26. Assessing the Evidence for Clinical Utility in Newborn Screening 517
Scott D. Grosse
27. The Role of Epidemiology in Assessing the Potential Clinical Impact
of Pharmacogenomics 533
David L. Veenstra
28. The Human Epigenome and Cancer 551
Mukesh Verma
29. The Use of Family History in Public Health Practice: The
Epidemiologic View 579
Rodolfo Valdez, Muin J. Khoury, and Paula W. Yoon
PART V Case Studies: Assessing the Use of Genetic
Information in Practice for Speci c Diseases
30. Cytochrome P450 Testing in the Treatment of Depression 597
Iris Grossman, Mugdha Thakur, and David B. Matchar
31. A Rapid-ACCE Review of CYP2C9 and VKORC1 Allele Testing to
Inform Warfarin Dosing in Adults at Elevated Risk for Thrombotic
Events to Avoid Serious Bleeding 620
Monica R. McClain, Glenn E. Palomaki, Margaret Piper, and
James E. Haddow
32. Hereditary Hemochromatosis: Population Screening for Gene Mutations 639
Diana B. Petitti
Index 657
xv
S R. B, BA, BFA
McKing Consulting Corporation
Of ce of Public Health Genomics

Centers for Disease Control and
Prevention
Atlanta, GA
A O. B, MD, MPH
Department of Family Medicine
University of Washington
Seattle, WA
J L. B, PD
Department of Epidemiology and
Biostatistics
Memorial Sloan-Kettering Cancer Center
New York, NY
L B, MD
Max-Planck Institute for Molecular Genetics
Berlin, Germany
N B, MD, MS
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
P B, MD
International Agency for Research on
Cancer
Lyon, France
M L. B, PD
Department of Epidemiology
University of Texas
M.D. Anderson Cancer Center
Houston, TX
L A. B, PD

Women & Infants Hospital
Department of Pathology and
Laboratory Medicine
The Warren Alpert Medical School of
Brown University
Providence, RI
M S. B, PD
Center for Human Genetics
Institute of Molecular Medicine and
School of Public Health
University of Texas
Houston, TX
P E. B, PD
Renal Research Laboratories
Manchester Institute of Nephrology and
Transplantation
Royal Inrmary
Manchester, United Kingdom
P B, PD
Foundation for Genomics and
Population Health (PHG Foundation)
Cambridge, United Kingdom
P A. B,
PD, MPH
Division of Epidemiology
University of California
Berkeley School of Public Health
Berkeley, CA
P R. B, MD
Department of Health Sciences

University of Leicester
Leicester, United Kingdom
Contributors
xvi

A S. B,
MS, PD
Department of Public Health and
Primary Care
University of Cambridge
Cambridge, United Kingdom
and
UK HuGENet Coordinating Centre
Cambridge, United Kingdom
N C, MD, MPH
Colorado Department of Public Health
and Environment
Denver, CO
H C, MD, FRCP,
FFPH, FRSE
Public Health Sciences
College of Medicine and Vet Medicine
University of Edinburgh
Edinburgh, United Kingdom
J P C, MD
Department of Epidemiology and
Population Health
London School of Hygiene and Tropical
Medicine
London, United Kingdom

S J. C, MD
Laboratory of Translational Genomics
Division of Cancer Epidemiology and
Genetics
National Cancer Institute, National
Institutes of Health
Bethesda, MD
A P. C,
PD, MS
Division of Epidemiology
School of Public Health
University of California at Berkeley
Berkeley, CA
B C, PD
Former Senior Editor
Public Library of Science
San Francisco, CA
J D, MD, MBCB,
MS, DP, FRCP
Department of Public Health and
Primary Care
University of Cambridge
Cambridge, United Kingdom
G D S, MD,
DS, FRCP, F M S
MRC Centre for Causal Analyses in
Translational Epidemiology
Department of Social Medicine
University of Bristol
Bristol, United Kingdom

A D, MS
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
S M. D, MD, MPH
Albert Einstein College of Medicine
Monte ore Medical Center
Bronx, NY
W. D D, PD
Of ce of Public Health Genomics
Centers for Disease Control and
Prevention
Atlanta, GA
M P. D, MS
McKing Consulting Corporation
Of ce of Public Health Genomics
Centers for Disease Control and
Prevention
Atlanta, GA
xvii
Contributors
C M.  D, PD
Department of Epidemiology
Erasmus University Medical Center
Rotterdam, The Netherlands
R D, PD, MA
Department of Dermatology
Leiden University Medical Center
Leiden, The Netherlands

S E, MS, DM,
FRCP, FFPHM
London School of Hygiene and Tropical
Medicine
London, United Kingdom
E  E, MD, MS
Institute of Social and Preventive
Medicine
University of Bern
Bern, Switzerland
and
German Cochrane Centre
Department of Medical Biometry and
Medical Informatics
University Medical Centre
Freiburg, Germany
J D. F, PD,
MPH
Division of Cancer Epidemiology and
Genetics
National Cancer Institute
Department of Health and Human
Services
Bethesda, MD
I F, PD
Public Population Project in Genomics
Montreal, QC, Canada
and
Department of Social and Preventive
Medicine

University of Montreal
Montreal, QC, Canada
M F, MD
Dana-Farber Cancer Institute
Boston, MA
H F, PD
University of North Carolina at Chapel
Hill
Chapel Hill, NC
F G, MS, PD
University of Toronto
Dalla Lana School of Public Health
Toronto, ON, Canada
M G-C,
MD, MPH, DPH
Division of Cancer Epidemiology and
Genetics
National Cancer Institute
Bethesda, MD
J G, PD, DS,
FMS
Paediatric and Perinatal Epidemiology
Bristol, United Kingdom
J G-B,
MD, PD
Laboratory of Translational Genomics
Division of Cancer Epidemiology and
Genetics
National Cancer Institute, National
Institutes of Health

Bethesda, MD
J G, MBCB,
PD, FRCGP
Canada Research Chair in Health
Knowledge Transfer and Uptake
Clinical Epidemiology Program
Ottawa Health Research Institute
Department of Medicine
University of Ottawa
Ottawa, ON, Canada
xviii

S D. G, PD
National Center on Birth Defects and
Developmental Disabilities
Centers for Disease Control and
Prevention
Atlanta, GA
I G, PD
Pharmacogenetics Consulting
Cabernet Pharmaceuticals
Durham, NC
N A. G, PD
Harvard School of Public Health
Boston, MA
J M. G, MS, MBA
Intermountain Healthcare
Clinical Genetics Institute
Salt Lake City, UT
M G, MD, MPH

Of ce of Public Health Genomics
Centers for Disease Control and
Prevention
Atlanta, GA
J E. H, MD
Department of Pathology and
Laboratory Medicine
Brown University, Alpert Medical School
Providence, RI
M H, PD
Gene–Environment Epidemiology Group
International Agency for Research on
Cancer
Lyon, France
S H, MS
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
J P. T. H, PD
MRC Biostatistics Unit
Institute of Public Health
Cambridge, United Kingdom
D J. H, MBBS, SD
Program in Molecular and Genetic
Epidemiology
Departments of Epidemiology and
Nutrition
Harvard School of Public Health
Boston, MA

K H, MS
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
C I-R,
MD, PD
Department of Epidemiology,
Biostatistics, and Occupational Health
Faculty of Medicine
McGill University
Montreal, QC, Canada
J P. A. I, MD, PD
Clinical and Molecular Epidemiology
Unit
Department of Hygiene and
Epidemiology
School of Medicine and Biomedical
Research Institute
Foundation for Research and
Technology-Hellas
University of Ioannina
Ioannina, Greece
and
Center for Genetic Epidemiology and
Modeling
Department of Medicine
Tufts University School of Medicine
Boston, MA
xix

Contributors
A. C J. W. J, PD
Department of Epidemiology
Erasmus University Medical Center
Rotterdam, The Netherlands
M-R J, MD,
MS, PD
Department of Epidemiology and Public
Health
Imperial College
London, United Kingdom
and
Department of Public Health Science and
General Practice
University of Oulu
Oulu, Finland
C Y. J, MS
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
M J. K, MD, PD
Of ce of Public Health Genomics
Centers for Disease Control and
Prevention
Atlanta, GA
and
Division of Cancer Control and
Population Sciences
National Cancer Institute

Bethesda, MD
R A. K, MD
Genetics in Medicine
Minneapolis, MN
B M. K,
PD, O.C.
Centre of Genomics and Policy
Department of Human Genetics
McGill University
Montreal, QC
P K, PD
Department of Epidemiology and
Biostatistics
Program in Molecular and Genetic
Epidemiology
Harvard School of Public Health
Boston, MA
J L, PD
Canada Research Chair in Human
Genome Epidemiology
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
B M,
MD, PD
Department of Radiation Sciences
Oncology
Umea University Hospital
Umea, Sweden

T M, MD, PD
Of ce of Population Genomics
National Human Genome Research
Institute
Bethesda, MD
D M. M,
MD
Department of Neurology
Mayo Clinic
Rochester, MN
xx

L M, PD, MS,
BS, RPHN
Department of Public Health
University of Aberdeen
Aberdeen, Scotland, United Kingdom
D B. M, MD
Duke Center for Clinical Health Policy
Research
Durham, NC
and
Department of Veterans Affairs Medical
Center
Durham, NC
and
Duke-NUS Graduate Medical School
Program in Health Services Research
Singapore
C M. MB, PD

Social and Behavioral Research Branch
National Human Genome Research
Institute
Washington, DC
M I. MC, MD,
FRCP, FMS
Oxford Centre for Diabetes,
Endocrinology and Metabolism
University of Oxford
Oxford, United Kingdom
and
Wellcome Trust Centre for Human
Genetics
University of Oxford
Oxford, United Kingdom
and
Oxford NIHR Biomedical Research
Centre
Churchill Hospital
Oxford, United Kingdom
M R. MC, PD
Division of Medical Screening
Women & Infants Hospital
Providence, RI
J ML, PD
Population Studies and Surveillance
Cancer Care Ontario
Toronto, ON, Canada
and
Prosserman Centre for Health Research

at the Samuel Lunenfeld Research
Institute
Toronto, ON, Canada
J B. J.  M, PD
Department of Internal Medicine
Erasmus MC
Rotterdam, The Netherlands
D M, PD
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
J A. N-B, PD
Genetic Epidemiology Division
CR-UK Clinical Centre
Leeds, United Kingdom
T R. O’B, MD, MPH
Division of Cancer Epidemiology and
Genetics
National Cancer Institute
Rockville, MD
J M. O, PD
Information Engineering Branch
National Center for Biotechnology
Information
National Library of Medicine, NIH
Bethesda, MD
R P. O, PD
PharmGKB
Genetics Department

Stanford University
Stanford, CA
xxi
Contributors
R A. P, MD
University of Washington
School of Medicine
Seattle, WA
G E. P, BS
Department of Pathology and
Laboratory Medicine
Brown University, Alpert
Medical School
Providence, RI
A P, MD
Genetics of Complex Diseases
Hospital for Sick Children (SickKids)
Toronto, ON, Canada
D B. P,
MD, MPH
Department of Biomedical
Informatics
Arizona State University
Phoenix, AZ
M P, PD
Blue Cross Blue Shield Association
Technology Evaluation Center
Chicago, IL
T R. R, PD
Center for Clinical Epidemiology and

Biostatistics
School of Medicine
University of Pennsylvania
Philadelphia, PA
E R, PD
International Agency for
Research on Cancer
Lyon, France
and
Imperial College
London, United Kingdom
F R, MD,
PD
Departments of Internal Medicine and
Epidemiology
Erasmus MC
Rotterdam, The Netherlands
N R, MD,
MPH, MHS
Division of Cancer Epidemiology and
Genetics
National Cancer Institute
Bethesda, MD
G S, PD
School of Medicine and Biomedical
Research Institute
University of Ioannina
Ioannina, Greece
N S, M, PD
Department of Public Health and

Primary Care
University of Cambridge
Cambridge, United Kingdom
S C. S, PD
Genetics and Genomic Sciences
Mount Sinai School of Medicine
New York, NY
P S, PD
MD Anderson Cancer Center
Department of Epidemiology
University of Texas
Houston, TX
D S, PD,
MPH
Epidemiology and Genetics Research
Program
Division of Cancer Control and
Population Sciences
National Cancer Institute, NIH
Bethesda, MD
xxii

L S, PD
National Cancer Registry (NCR)
Cork, Ireland, United Kingdom
A S, PD,
BSH, MS
University of Ottawa Heart Institute
Ottawa, ON, Canada
E T, MD, PD

University of Pittsburgh Cancer Institute
University of Pittsburgh Medical Center
Pittsburgh, PA
V T, PD
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
S M. T, MD,
MPH
Los Angeles County Department of
Public Health
Los Angeles, CA
M T, MD
Department of Psychiatry and
Behavioral Sciences
Duke University Medical Center
Durham, NC
E T, PD
Public Health Sciences
University of Edinburgh
Edinburgh, Scotland, United Kingdom
D C. T, PD
Biostatistics Division
Verna Richter Chair in Cancer Research
Department of Preventive Medicine
University of Southern California
Los Angeles, CA
N T, PD
Department of Social Medicine

University of Bristol
Bristol, United Kingdom
Aé G. U, PD
Departments of Internal Medicine and
Epidemiology
Erasmus MC
Rotterdam, The Netherlands
R V, PD, MS
Of ce of Public Health Genomics
Centers for Disease Control and
Prevention
Atlanta, GA
D L. V, PD,
PD
Pharmaceutical Outcomes Research
and Policy Program, and Institute for
Public Health Genetics
University of Washington
Seattle, WA
M V, PD
Methods and Technologies Branch
Epidemiology and Genetics Research
Program
Division of Cancer Control and
Population Sciences
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Bethesda, MD
P V, MD, MPH
Environmental Epidemiology

Imperial College
London, United Kingdom
xxiii
Contributors
C H. W, PD,
MPH
Social and Behavioral Research Branch
& Genome Technology Branch
National Human Genome Research
Institute
Washington, DC
N W, PD, MRC
Medical Research Council Epidemiology
Unit
Elsie Widdowson Laboratories
Cambridge, United Kingdom
G W, MS, PD
Cardiovascular Research Methods
Centre
University of Ottawa Heart Institute
Ottawa, ON, Canada
M W, BS MS
Department of Epidemiology and
Community Medicine
University of Ottawa
Ottawa, ON, Canada
M S. W, MD
Intermountain Healthcare
Clinical Genetics Institute
Salt Lake City, UT

R E. W, PD
American Journal of Human Genetics
Boston, MA
D M. W, PD
Division of Cancer Control and
Population Sciences
National Cancer Institute
Bethesda, MD
P W. Y, SD, MPH
Division for Heart Disease and Stroke
Prevention
Centers for Disease Control and
Prevention
Atlanta, GA
W Y, PD, MS
Of ce of Public Health Genomics
Centers for Disease Control and
Prevention
Atlanta, GA
M Z, PD, MPH
Lancet
New York, NY
R Z, MA, FRCP,
FFPHM
Foundation for Genomics and
Population Health (PHG Foundation)
Cambridge, United Kingdom
G Y Z, PD
Department of Epidemiology and
Biostatistics

University of Western Ontario
London, ON, Canada
and
Robarts Clinical Trials
Robarts Research Institute
London, ON, Canada
E Z, PD
Wellcome Trust Centre for Human
Genetics
University of Oxford
Oxford, United Kingdom
and
Wellcome Trust Sanger Institute
Wellcome Trust Genome Campus
Cambridge, United Kingdom
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