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Human Genome Epidemiology 2nd edition book cover

Human Genome Epidemiology (2^nd ed.): 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, and Julian Little

“The findings and conclusions in this book are those of the author(s) and do not necessarily represent the views of the funding agency.”

These chapters were published with modifications by Oxford University Press (2010)

Copyright

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OXFORD UNIVERSITY PRESS
2010
Oxford University Press
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Preface

In the first edition of Human Genome Epidemiology published in 2004, we discussed how the epidemiologic approach provides an important scientific foundation for studying the continuum from gene discovery to the development, applications, and evaluation of human genome information in improving health and preventing disease. Since 2004, advances in human genomics have continued to occur at a breathtaking pace. Although the concept of personalized healthcare and disease prevention often promised by enthusiastic scientists and the media is yet to be fulfilled, we are now seeing progress and rapid accumulation of data in many “omics” related research fields. 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 influences of genetic and environmental factors on the occurrence of common diseases.
With all these ongoing developments, we have invited many authors who are leaders in the field to produce the second edition of Human Genome Epidemiology. Our aim is to inform readers of new developments in the genomics field and how epidemiologic 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 We do realize that the material presented in this book will be outdated even before it is published.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 first edition of Human Genome Epidemiology.
This new edition is divided into five parts. In Part I, we revisit the fundamentals of human genome epidemiology. We first 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 field 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 synthesis 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 consortia 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 (Chapter 10), evolving methods for integrating the evidence (Chapter 11) as well as assessment of cumulative evidence and field 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 publication 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 leukemia (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 specific 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 occurrence of human diseases using data on the association of genetic variation and disease 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 profiles) 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 briefly summarizes how reviews of the evidence 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, Chapter 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 treatment of depression with SSRIs (Chapter 30) and warfarin therapy (Chapter 31). We also present information on population screening for hereditary hemochromatosis (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 common 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 find 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-first century.
Atlanta MJK, SB, MG
Cambridge JH
Ioannina JI
Ottawa JL
2009

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Acknowledgments

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
John Thompson
Rodolfo Valdez
Jan Vandenbroucke
David Veenstra
Bridget Wilcken
Lauren E. Williams
Quanhe Yang
Ajay Yesupriya
Wei Yu

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Part I - Fundamentals of Human Genome Epidemiology Revisited

Human genome epidemiology: The road map revisited
Muin J. Khoury, Sara R. Bedrosian, Marta L. Gwinn, Julian P. T. Higgins, John P. A. Ioannidis, and Julian Little
Principles of analysis of germline genetics
Jesus Gonzalez-Bosquet and Stephen J. Chanock
The public health genomics enterprise
Philippa Brice and Ron Zimmern
Navigating the evolving knowledge of human genetic variation in health and disease
Marta L. Gwinn and Wei Yu

Part II - Methods and Approaches for Data Collection, Analysis, and Integration

The global emergence of epidemiological biobanks: Opportunities and challenges
Paul R. Burton, Isabel Fortier, and Bartha Knoppers
Case-control and cohort studies in the age of genome-wide associations
Teri Manolio
The emergence of networks in human genome epidemiology: Challenges and opportunities
Daniela Seminara, Muin J. Khoury, Thomas R. O’Brien, Teri Manolio, Marta L. Gwinn, Julian Little, Julian P. T. Higgins, Jonine L. Bernstein, Paolo Boffetta, Melissa L. Bondy, Molly S. Bray, Paul E. Brenchley, Patricia A. Bufﬂer, Juan Pablo Casas, Anand P. Chokkalingam, John Danesh, 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, Andre´ G. Uitterlinden, Paolo Vineis, Nick Wareham, Deborah M. Winn, Ron Zimmern, and John P. A. Ioannidis
Design and analysis issues in genome-wide association studies
Duncan C. Thomas
The challenge of assessing complex gene–gene and gene–environment interactions
Peter Kraft and David J. Hunter
STrengthening the REporting of Genetic Association Studies (STREGA)—An extension of the STROBE statement
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 L. Gwinn, Robin E. Williamson, Guang Yong Zou, Kimberley Hutchings, Candice Y. Johnson, Valerie Tait, Miriam Wiens, Jean Golding, Cornelia 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
Integration of the evidence on gene-disease associations: Methods of HuGE reviews
Julian P.T. Higgins and Julian Little
Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human disease
Muin J. Khoury, Lars Bertram, Paolo Boffetta, Adam S. Butterworth, Stephen J. Chanock, Siobhan M. Dolan, Isabel Fortier, Montserrat Garcia-Closas, Marta L. 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

PART III - Case Studies: Cumulative Assessment of the Role of Human Genome Variation in Specific Diseases

Colorectal cancer
Harry Campbell, Steven Hawken, Evropi Theodoratou, Alex Demarsh, Kimberley Hutchings, Candice Y. Johnson, Lindsey Masson, Linda Sharp, Valerie Tait, and Julian Little
Childhood leukemias
Anand P. Chokkalingam and Patricia A. Buffler
Bladder cancer
Jonine D. Figueroa, Montserrat Garcia-Closas, and Nathaniel Rothman
Type 2 diabetes
Eleftheria Zeggini and Mark I. McCarthy
Osteoporosis
André G. Uitterlinden, Joyce B.J. van Meurs, and Fernando Rivadeneira
Preterm birth
Siobhan M. Dolan
Coronary heart disease
Adam S. Butterworth, Julian P.T. Higgins, Nadeem Sarwar, and John Danesh
Schizophrenia
Lars Bertram

Part IV - Applications of Epidemiologic Methods for Using Genetic Information in Medicine and Public Health

Mendelian randomization: The contribution to genetic epidemiology to elucidating environmentally modifiable causes of disease
George Davey-Smith and Shah Ebrahim
Evaluation of predictive genetic tests for common diseases: Bridging epidemiological, clinical, and public health measures
A. Cecile J. W. Janssens, Marta Gwinn, and Muin J. Khoury
The Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) initiative: Methods of the EGAPP™ working group
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
Rapid evidence-based reviews of genetic tests
James M. Gudgeon, Glenn E. Palomaki, and Marc S. Williams
Role of social and behavioral research in assessing the utility of genetic information
Saskia C. Sanderson , Christopher Wade , and Colleen M. McBride
Assessing the evidence for clinical utility in newborn screening
Scott D. Grosse
The role of epidemiology in assessing the potential clinical impact of pharmacogenomics
David L. Veenstra
The human epigenome and cancer
Mukesh Verma
The use of family history in public health practice: the epidemiologic view
Rodolfo Valdez, Muin J. Khoury, and Paula W. Yoon

Part V - Case Studies: Assessing the Use of Genetic Information in Practice for Specific Diseases

Cytochrome P450 testing in the treatment of depression
Iris Grossman, Mugdha Thakur, and David B. Matchar
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
Monica R. McClain , Glenn E. Palomaki, Margaret Piper, and James E. Haddow
Hereditary hemochromatosis: Population screening for gene mutations
Diana B. Petitti

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Contributors
Sara R. Bedrosian, BA, BFA McKing Consulting Corporation Office of Public Health Genomics Centers for Disease Control and Prevention Atlanta, GA Alfred O. Berg, MD, MPH Department of Family Medicine University of Washington Seattle, WA Jonine L. Bernstein, PhD Department of Epidemiology and Biostatistics Memorial Sloan-Kettering Cancer Center New York, NY Lars Bertram, MD Max-Planck Institute for Molecular Genetics Berlin, Germany Nick Birkett, MD, MSc Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada Paolo Boffetta, MD International Agency for Research on Cancer Lyon, France Melissa L. Bondy, PhD Department of Epidemiology University of Texas M.D. Anderson Cancer Center Houston, TX Linda A. Bradley, PhD Women & Infants Hospital Department of Pathology and Laboratory Medicine The Warren Alpert Medical School of Brown University Providence, RI Molly S. Bray, PhD Center for Human Genetics Institute of Molecular Medicine and School of Public Health University of Texas Houston, TX Paul E. Brenchley, PhD Renal Research Laboratories Manchester Institute of Nephrology and Transplantation Royal Inﬁrmary Manchester, United Kingdom Philippa Brice, PhD Foundation for Genomics and Population Health (PHG Foundation)Cambridge, United Kingdom Patricia A. Buffler, PhD, MPH Division of Epidemiology University of California Berkeley School of Public Health Berkeley, CA Paul R. Burton, MD Department of Health Sciences University of Leicester Leicester, United Kingdom Adam S. Butterworth, MSc, PhD Department of Public Health and Primary Care University of Cambridge Cambridge, United Kingdom and UK HuGENet Coordinating Centre Cambridge, United Kingdom Ned Calonge, MD, MPH Colorado Department of Public Health and Environment Denver, CO Harry Campbell, MD, FRCP, FFPH, FRSE Public Health Sciences College of Medicine and Vet Medicine University of Edinburgh Edinburgh, United Kingdom Juan Pablo Casas, MD Department of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London, United Kingdom Stephen J. Chanock, MD Laboratory of Translational Genomics Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Bethesda, MD Anand P. Chokkalingam, PhD, MS Division of Epidemiology School of Public Health University of California at Berkeley Berkeley, CA Barbara Cohen, PhD Former Senior Editor Public Library of Science San Francisco, CA John Danesh, MD, MBChB, MSc, DPhil, FRCP Department of Public Health and Primary Care University of Cambridge Cambridge, United Kingdom George Davey Smith, MD, DSc, FRCP, F Med Sci MRC Centre for Causal Analyses in Translational Epidemiology Department of Social Medicine University of Bristol Bristol, United Kingdom Alex Demarsh, MSc Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada Siobhan M. Dolan, MD, MPH Albert Einstein College of Medicine Montefiore Medical Center Bronx, NY W. David Dotson, PhD Office of Public Health Genomics Centers for Disease Control and Prevention Atlanta, GA Michael P. Douglas, MS McKing Consulting Corporation Office of Public Health Genomics Centers for Disease Control and Prevention Atlanta, GA Cornelia M. van Duijn, PhD Professor of Genetic Epidemiology Department of Epidemiology Erasmus University Medical Center Rotterdam, The Netherlands Ross Duncan, PhD, MA Department of Dermatology Leiden University Medical Center Leiden, The Netherlands Shah Ebrahim, MSc,DM,FRCP,FFPHM London School of Hygiene and Tropical Medicine London, United Kingdom Erik von Elm, MD, MSc 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 Jonine D. Figueroa, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute Department of Health and Human Services Bethesda, MD Isabel Fortier, PhD Public Population Project in Genomics Montreal, QC, Canada and Department of Social and Preventive Medicine University of Montreal Montreal, QC, Canada Matthew Freedman, MD Dana-Farber Cancer Institute Boston, MA Helena Furberg, PhD University of North Carolina at Chapel Hill Chapel Hill, NC France Gagnon, MSc, PhDUniversity of Toronto Dalla Lana School of Public Health Toronto, ON, Canada Montserrat Garcia-Closas, MD, MPH, DrPH Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Bethesda, MD Jean Golding, PhD, DSc, FMedSci Paediatric and Perinatal Epidemiology Bristol, United Kingdom Jesus Gonzalez-Bosquet, MD, PhD Laboratory of Translational Genomics Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Bethesda, MD Jeremy Grimshaw, MBChB, PhD, 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 Scott D. Grosse, PhD National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention Atlanta, GA Iris Grossman, PhD Pharmacogenetics Consulting Cabernet Pharmaceuticals Durham, NC Nelleke A. Gruis, PhD Harvard School of Public Health Boston, MA James M. Gudgeon, MS, MBA Intermountain Healthcare Clinical Genetics Institute Salt Lake City, UT Marta Gwinn, MD, MPH McKing Consulting Corporation Office of Public Health Genomics Centers for Disease Control and Prevention Atlanta, GA James E. Haddow, MD Department of Pathology and Laboratory Medicine Brown University, Alpert Medical School Providence, RI Mia Hashibe, PhD Gene–Environment Epidemiology Group International Agency for Research on Cancer Lyon, France Steven Hawken, MSc Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada Julian P.T. Higgins, PhD MRC Biostatistics Unit Institute of Public Health Cambridge, United Kingdom and UK HuGENet Coordinating Centre Cambridge, United Kingdom David J. Hunter, MBBS, ScD Program in Molecular and Genetic Epidemiology Departments of Epidemiology and Nutrition Harvard School of Public Health Boston, MA Kimberley Hutchings, MSc Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada Claire Infante-Rivard, MD, PhD Department of Epidemiology, Biostatistics, and Occupational Health Faculty of Medicine McGill University Montréal, QC, Canada John P.A. Ioannidis, MD, PhD 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 Cecile J.W. Janssens, PhD Associate Professor of Epidemiology Department of Epidemiology Erasmus University Medical Center Rotterdam, The Netherlands Marjo-Riitta Jarvelin, MD, MSc, PhD 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 Candice Y. Johnson, MSc Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada	Muin J. Khoury, MD, PhD Office 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 Richard A. King, MD Genetics in Medicine Minneapolis, MN Bartha Knoppers, PhD, O.C. Centre of Genomics and Policy Department of Human Genetics McGill University Montreal, QC, Canada Peter Kraft, PhD Department of Epidemiology and Biostatistics Program in Molecular and Genetic Epidemiology Harvard School of Public Health Boston, MA Julian Little, PhD Canada Research Chair in Human Genome Epidemiology Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada Beatrice Malmer, MD, PhD Department of Radiation Sciences Oncology Umea University Hospital Umea, Sweden Teri Manolio, MD, PhD Office of Population Genomics National Human Genome Research Institute Bethesda, MD Demetrius M. Maraganore, MD Department of Neurology Mayo Clinic Rochester, MN Lindsey Masson, PhD, MSc, BSc, RPHNutr Department of Public Health University of Aberdeen Aberdeen, Scotland, United Kingdom David B. Matchar, 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 Colleen M. McBride, PhD Social and Behavioral Research Branch National Human Genome Research Institute Washington, DC Mark I. McCarthy, MD, FRCP, FMedSci 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 Monica R. McClain, PhD Division of Medical Screening Women & Infants Hospital Providence, RI John McLaughlin, PhD 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 Joyce B.J. van Meurs, PhD Department of Internal Medicine Erasmus Medical Center Rotterdam, The Netherlands David Moher, PhD Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada Julia A. Newton-Bishop, PhD Genetic Epidemiology Division CR-UK Clinical Centre Leeds, United Kingdom Thomas R. O’Brien, MD, MPH Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville, MD James M. Ostell, PhD Information Engineering Branch National Center for Biotechnology Information National Library of Medicine, National Institutes of Health Bethesda, MD Ryan P. Owen, PhD PharmGKB Genetics Department Stanford University Stanford, CA Roberta A. Pagon, MD University of Washington School of Medicine Seattle, WA Glenn E. Palomaki, BS Department of Pathology and Laboratory Medicine Brown University, Alpert Medical School Providence, RI Andrew Paterson, MD Genetics of Complex Diseases Hospital for Sick Children (SickKids) Toronto, ON, Canada Diana B. Petitti, MD, MPH Department of Biomedical Informatics Arizona State University Phoenix, AZ Margaret Piper, PhD Technology Evaluation Center Blue Cross Blue Shield Association Chicago, IL Timothy R. Rebbeck, PhD Center for Clinical Epidemiology and Biostatistics School of Medicine University of Pennsylvania Philadelphia, PA Elio Riboli, PhD International Agency for Research on Cancer Lyon, France and Imperial College London, United Kingdom Fernando Rivadeneira, MD, PhD Departments of Internal Medicine and Epidemiology Erasmus MC Rotterdam, The Netherlands Nathaniel Rothman, MD, MPH, MHS Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Bethesda, MD Georgia Salanti, PhD School of Medicine and Biomedical Research Institute University of Ioannina Ioannina, Greece Nadeem Sarwar, MPhil, PhD Department of Public Health and Primary Care University of Cambridge Cambridge, United Kingdom Saskia C. Sanderson, PhD Genetics and Genomic Sciences Mount Sinai School of Medicine New York, NY Paul Scheet, PhD MD Anderson Cancer Center Department of Epidemiology University of Texas Houston, TX Daniela Seminara, PhD, MPH Epidemiology and Genetics Research Program Division of Cancer Control and Population Sciences National Cancer Institute, NIH Bethesda, MD Linda Sharp, PhD National Cancer Registry (NCR) Cork, Ireland, United Kingdom Alexandre Stewart, PhD, BScH, MSc University of Ottawa Heart Institute Ottawa, ON, Canada Emanuela Taioli, MD, PhD University of Pittsburgh Cancer Institute University of Pittsburgh Medical Center Pittsburgh, PA Valerie Tait, PhD Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada Steven M. Teutsch, MD, MPH Los Angeles County Department of Public Health Los Angeles, CA Mugdha Thakur, MD Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham, NC Evropi Theodoratou, PhD Public Health Sciences University of Edinburgh Edinburgh, Scotland, United Kingdom Duncan C. Thomas, PhD Biostatistics Division Verna Richter Chair in Cancer Research Department of Preventive Medicine University of Southern California Los Angeles, CA Nic Timpson, PhD Department of Social Medicine University of Bristol Bristol, United Kingdom Andre´ G. Uitterlinden, PhD Departments of Internal Medicine and Epidemiology & Biostatistics Erasmus MC Rotterdam, The Netherlands Rodolfo Valdez, PhD, MSc Office of Public Health Genomics Centers for Disease Control and Prevention Atlanta, GA David L. Veenstra, PhD, PharmD Pharmaceutical Outcomes Research and Policy Program and Institute for Public Health Genetics University of Washington Seattle, WA Mukesh Verma, PhD 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 Paolo Vineis, MD, MPH Environmental Epidemiology Imperial College London, United Kingdom Christopher Wade, PhD, MPH Social and Behavioral Research Branch & Genome Technology Branch National Human Genome Research Institute Washington, DC Nick Wareham, PhD, MRC Medical Research Council Epidemiology Unit Elsie Widdowson Laboratories Cambridge, United Kingdom George Wells, MSc, PhD Cardiovascular Research Methods Centre University of Ottawa Heart Institute Ottawa, ON, Canada Miriam Wiens, BSc MSc Department of Epidemiology and Community Medicine University of Ottawa Ottawa, ON, Canada Marc S. Williams, MD Intermountain Healthcare Clinical Genetics Institute Salt Lake City, UT Robin E. Williamson, PhD Deputy Editor American Journal of Human Genetics Boston, MA Deborah M. Winn, PhD Division of Cancer Control and Population Sciences National Cancer Institute Bethesda, MD Paula W. Yoon, ScD, MPH Division for Heart Disease and Stroke Prevention Centers for Disease Control and Prevention Atlanta, GA Wei Yu, PhD, MS Office of Public Health Genomics Centers for Disease Control and Prevention Atlanta, GA Maja Zecevic, PhD, MPH Senior Editor Lancet New York, NY Ron Zimmern, MA, FRCP, FFPHM Foundation for Genomics and Population Health (PHG Foundation) Cambridge, United Kingdom Guang Yong Zou, PhD Department of Epidemiology and Biostatistics University of Western Ontario London, ON, Canada and Robarts Clinical Trials Robarts Research Institute London, ON, Canada Eleftheria Zeggini, PhD Wellcome Trust Centre for Human Genetics University of Oxford, Oxford, United Kingdom and Wellcome Trust Sanger Institute Wellcome Trust Genome Campus Cambridge, United Kingdom

Contributors

Sara R. Bedrosian, BA, BFA
McKing Consulting Corporation
Office of Public Health Genomics
Centers for Disease Control and
Prevention
Atlanta, GA
Alfred O. Berg, MD, MPH
Department of Family Medicine
University of Washington
Seattle, WA
Jonine L. Bernstein, PhD
Department of Epidemiology and Biostatistics
Memorial Sloan-Kettering Cancer Center New York, NY
Lars Bertram, MD
Max-Planck Institute for Molecular Genetics
Berlin, Germany
Nick Birkett, MD, MSc
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada
Paolo Boffetta, MD
International Agency for Research on Cancer
Lyon, France
Melissa L. Bondy, PhD
Department of Epidemiology
University of Texas
M.D. Anderson Cancer Center
Houston, TX
Linda A. Bradley, PhD
Women & Infants Hospital
Department of Pathology and Laboratory Medicine
The Warren Alpert Medical School of Brown University
Providence, RI
Molly S. Bray, PhD
Center for Human Genetics
Institute of Molecular Medicine and School of Public Health
University of Texas
Houston, TX
Paul E. Brenchley, PhD
Renal Research Laboratories
Manchester Institute of Nephrology and Transplantation
Royal Inﬁrmary
Manchester, United Kingdom
Philippa Brice, PhD
Foundation for Genomics and
Population Health (PHG Foundation)Cambridge, United Kingdom
Patricia A. Buffler, PhD, MPH
Division of Epidemiology
University of California
Berkeley School of Public Health
Berkeley, CA
Paul R. Burton, MD
Department of Health Sciences
University of Leicester
Leicester, United Kingdom
Adam S. Butterworth, MSc, PhD
Department of Public Health and Primary Care
University of Cambridge
Cambridge, United Kingdom
and
UK HuGENet Coordinating Centre
Cambridge, United Kingdom
Ned Calonge, MD, MPH
Colorado Department of Public Health and Environment
Denver, CO
Harry Campbell, MD, FRCP, FFPH, FRSE
Public Health Sciences
College of Medicine and Vet Medicine
University of Edinburgh
Edinburgh, United Kingdom
Juan Pablo Casas, MD
Department of Epidemiology and Population Health
London School of Hygiene and Tropical Medicine
London, United Kingdom
Stephen J. Chanock, MD
Laboratory of Translational Genomics
Division of Cancer Epidemiology and Genetics
National Cancer Institute, National Institutes of Health
Bethesda, MD
Anand P. Chokkalingam, PhD, MS
Division of Epidemiology
School of Public Health
University of California at Berkeley
Berkeley, CA
Barbara Cohen, PhD
Former Senior Editor
Public Library of Science
San Francisco, CA
John Danesh, MD, MBChB, MSc, DPhil, FRCP
Department of Public Health and Primary Care
University of Cambridge
Cambridge, United Kingdom
George Davey Smith, MD, DSc, FRCP,
F Med Sci
MRC Centre for Causal Analyses in
Translational Epidemiology
Department of Social Medicine
University of Bristol
Bristol, United Kingdom
Alex Demarsh, MSc
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada
Siobhan M. Dolan, MD, MPH
Albert Einstein College of Medicine
Montefiore Medical Center
Bronx, NY
W. David Dotson, PhD
Office of Public Health Genomics
Centers for Disease Control and Prevention
Atlanta, GA
Michael P. Douglas, MS
McKing Consulting Corporation
Office of Public Health Genomics
Centers for Disease Control and Prevention
Atlanta, GA
Cornelia M. van Duijn, PhD
Professor of Genetic Epidemiology
Department of Epidemiology
Erasmus University Medical Center
Rotterdam, The Netherlands
Ross Duncan, PhD, MA
Department of Dermatology
Leiden University Medical Center
Leiden, The Netherlands
Shah Ebrahim, MSc,DM,FRCP,FFPHM
London School of Hygiene and Tropical Medicine
London, United Kingdom
Erik von Elm, MD, MSc
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
Jonine D. Figueroa, PhD
Division of Cancer Epidemiology and Genetics
National Cancer Institute
Department of Health and Human Services
Bethesda, MD
Isabel Fortier, PhD
Public Population Project in Genomics
Montreal, QC, Canada
and
Department of Social and Preventive
Medicine
University of Montreal
Montreal, QC, Canada
Matthew Freedman, MD
Dana-Farber Cancer Institute
Boston, MA
Helena Furberg, PhD
University of North Carolina at Chapel Hill
Chapel Hill, NC
France Gagnon, MSc, PhDUniversity of Toronto
Dalla Lana School of Public Health
Toronto, ON, Canada
Montserrat Garcia-Closas, MD, MPH, DrPH
Division of Cancer Epidemiology and Genetics
National Cancer Institute, National Institutes of Health
Bethesda, MD
Jean Golding, PhD, DSc, FMedSci
Paediatric and Perinatal Epidemiology
Bristol, United Kingdom
Jesus Gonzalez-Bosquet, MD, PhD
Laboratory of Translational Genomics
Division of Cancer Epidemiology and Genetics
National Cancer Institute, National Institutes of Health
Bethesda, MD
Jeremy Grimshaw, MBChB, PhD, 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
Scott D. Grosse, PhD
National Center on Birth Defects and Developmental Disabilities
Centers for Disease Control and Prevention
Atlanta, GA
Iris Grossman, PhD
Pharmacogenetics Consulting
Cabernet Pharmaceuticals
Durham, NC
Nelleke A. Gruis, PhD
Harvard School of Public Health
Boston, MA
James M. Gudgeon, MS, MBA
Intermountain Healthcare Clinical Genetics Institute
Salt Lake City, UT
Marta Gwinn, MD, MPH
McKing Consulting Corporation
Office of Public Health Genomics
Centers for Disease Control and Prevention
Atlanta, GA
James E. Haddow, MD
Department of Pathology and Laboratory Medicine
Brown University, Alpert Medical School
Providence, RI
Mia Hashibe, PhD
Gene–Environment Epidemiology Group
International Agency for Research on Cancer
Lyon, France
Steven Hawken, MSc
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada
Julian P.T. Higgins, PhD
MRC Biostatistics Unit
Institute of Public Health
Cambridge, United Kingdom
and
UK HuGENet Coordinating Centre
Cambridge, United Kingdom
David J. Hunter, MBBS, ScD
Program in Molecular and Genetic Epidemiology
Departments of Epidemiology and Nutrition
Harvard School of Public Health
Boston, MA
Kimberley Hutchings, MSc
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada
Claire Infante-Rivard, MD, PhD
Department of Epidemiology, Biostatistics, and Occupational Health
Faculty of Medicine
McGill University
Montréal, QC, Canada
John P.A. Ioannidis, MD, PhD
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
Cecile J.W. Janssens, PhD
Associate Professor of Epidemiology
Department of Epidemiology
Erasmus University Medical Center
Rotterdam, The Netherlands
Marjo-Riitta Jarvelin, MD, MSc, PhD
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
Candice Y. Johnson, MSc
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada

Muin J. Khoury, MD, PhD
Office 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
Richard A. King, MD
Genetics in Medicine
Minneapolis, MN
Bartha Knoppers, PhD, O.C.
Centre of Genomics and Policy
Department of Human Genetics
McGill University
Montreal, QC, Canada
Peter Kraft, PhD
Department of Epidemiology and Biostatistics
Program in Molecular and Genetic Epidemiology
Harvard School of Public Health
Boston, MA
Julian Little, PhD
Canada Research Chair in Human
Genome Epidemiology
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada
Beatrice Malmer, MD, PhD
Department of Radiation Sciences
Oncology
Umea University Hospital
Umea, Sweden
Teri Manolio, MD, PhD
Office of Population Genomics
National Human Genome Research Institute
Bethesda, MD
Demetrius M. Maraganore, MD
Department of Neurology
Mayo Clinic
Rochester, MN
Lindsey Masson, PhD, MSc, BSc, RPHNutr
Department of Public Health
University of Aberdeen
Aberdeen, Scotland, United Kingdom
David B. Matchar, 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
Colleen M. McBride, PhD
Social and Behavioral Research Branch
National Human Genome Research Institute
Washington, DC
Mark I. McCarthy, MD, FRCP, FMedSci
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
Monica R. McClain, PhD
Division of Medical Screening
Women & Infants Hospital
Providence, RI
John McLaughlin, PhD
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
Joyce B.J. van Meurs, PhD
Department of Internal Medicine
Erasmus Medical Center
Rotterdam, The Netherlands
David Moher, PhD
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada
Julia A. Newton-Bishop, PhD
Genetic Epidemiology Division
CR-UK Clinical Centre
Leeds, United Kingdom
Thomas R. O’Brien, MD, MPH
Division of Cancer Epidemiology and Genetics
National Cancer Institute
Rockville, MD
James M. Ostell, PhD
Information Engineering Branch
National Center for Biotechnology Information
National Library of Medicine, National Institutes of Health
Bethesda, MD
Ryan P. Owen, PhD
PharmGKB Genetics Department
Stanford University
Stanford, CA
Roberta A. Pagon, MD
University of Washington
School of Medicine
Seattle, WA
Glenn E. Palomaki, BS
Department of Pathology and Laboratory Medicine
Brown University, Alpert
Medical School
Providence, RI
Andrew Paterson, MD
Genetics of Complex Diseases
Hospital for Sick Children (SickKids)
Toronto, ON, Canada
Diana B. Petitti, MD, MPH
Department of Biomedical Informatics
Arizona State University
Phoenix, AZ
Margaret Piper, PhD
Technology Evaluation Center
Blue Cross Blue Shield Association
Chicago, IL
Timothy R. Rebbeck, PhD
Center for Clinical Epidemiology and Biostatistics
School of Medicine
University of Pennsylvania
Philadelphia, PA
Elio Riboli, PhD
International Agency for Research on Cancer
Lyon, France
and
Imperial College
London, United Kingdom
Fernando Rivadeneira, MD, PhD
Departments of Internal Medicine and Epidemiology Erasmus MC
Rotterdam, The Netherlands
Nathaniel Rothman, MD, MPH, MHS
Division of Cancer Epidemiology and Genetics
National Cancer Institute, National Institutes of Health
Bethesda, MD
Georgia Salanti, PhD
School of Medicine and Biomedical Research Institute
University of Ioannina
Ioannina, Greece
Nadeem Sarwar, MPhil, PhD
Department of Public Health and Primary Care
University of Cambridge
Cambridge, United Kingdom
Saskia C. Sanderson, PhD
Genetics and Genomic Sciences
Mount Sinai School of Medicine
New York, NY
Paul Scheet, PhD
MD Anderson Cancer Center
Department of Epidemiology
University of Texas
Houston, TX
Daniela Seminara, PhD, MPH
Epidemiology and Genetics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute, NIH
Bethesda, MD
Linda Sharp, PhD
National Cancer Registry (NCR)
Cork, Ireland, United Kingdom
Alexandre Stewart, PhD, BScH, MSc
University of Ottawa Heart Institute
Ottawa, ON, Canada
Emanuela Taioli, MD, PhD
University of Pittsburgh Cancer Institute
University of Pittsburgh Medical Center
Pittsburgh, PA
Valerie Tait, PhD
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada
Steven M. Teutsch, MD, MPH
Los Angeles County Department of
Public Health
Los Angeles, CA

Mugdha Thakur, MD
Department of Psychiatry and Behavioral Sciences
Duke University Medical Center
Durham, NC
Evropi Theodoratou, PhD
Public Health Sciences
University of Edinburgh
Edinburgh, Scotland, United Kingdom
Duncan C. Thomas, PhD
Biostatistics Division
Verna Richter Chair in Cancer Research
Department of Preventive Medicine
University of Southern California
Los Angeles, CA
Nic Timpson, PhD
Department of Social Medicine
University of Bristol
Bristol, United Kingdom
Andre´ G. Uitterlinden, PhD
Departments of Internal Medicine and Epidemiology & Biostatistics
Erasmus MC
Rotterdam, The Netherlands
Rodolfo Valdez, PhD, MSc
Office of Public Health Genomics
Centers for Disease Control and Prevention
Atlanta, GA
David L. Veenstra, PhD, PharmD
Pharmaceutical Outcomes Research and Policy Program and Institute for Public Health Genetics
University of Washington
Seattle, WA
Mukesh Verma, PhD
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
Paolo Vineis, MD, MPH
Environmental Epidemiology
Imperial College
London, United Kingdom
Christopher Wade, PhD, MPH
Social and Behavioral Research Branch & Genome Technology Branch
National Human Genome Research Institute
Washington, DC
Nick Wareham, PhD, MRC
Medical Research Council Epidemiology Unit
Elsie Widdowson Laboratories
Cambridge, United Kingdom
George Wells, MSc, PhD
Cardiovascular Research Methods Centre
University of Ottawa Heart Institute
Ottawa, ON, Canada
Miriam Wiens, BSc MSc
Department of Epidemiology and Community Medicine
University of Ottawa
Ottawa, ON, Canada
Marc S. Williams, MD
Intermountain Healthcare Clinical Genetics Institute
Salt Lake City, UT
Robin E. Williamson, PhD
Deputy Editor
American Journal of Human Genetics
Boston, MA
Deborah M. Winn, PhD
Division of Cancer Control and Population Sciences
National Cancer Institute
Bethesda, MD
Paula W. Yoon, ScD, MPH
Division for Heart Disease and Stroke Prevention
Centers for Disease Control and Prevention
Atlanta, GA
Wei Yu, PhD, MS
Office of Public Health Genomics
Centers for Disease Control and Prevention
Atlanta, GA
Maja Zecevic, PhD, MPH
Senior Editor
Lancet
New York, NY
Ron Zimmern, MA, FRCP, FFPHM
Foundation for Genomics and
Population Health (PHG Foundation)
Cambridge, United Kingdom
Guang Yong Zou, PhD
Department of Epidemiology and Biostatistics
University of Western Ontario
London, ON, Canada
and
Robarts Clinical Trials
Robarts Research Institute
London, ON, Canada
Eleftheria Zeggini, PhD
Wellcome Trust Centre for Human Genetics
University of Oxford,
Oxford, United Kingdom
and
Wellcome Trust Sanger Institute
Wellcome Trust Genome Campus
Cambridge, United Kingdom

Suggested Citation:

Khoury MJ, Bedrosian S, Gwinn M, Higgins JPT, Ioannidis JPA, Little J, editors. Human Genome Epidemiology (Second Edition): Building the evidence for using genetic information to improve health and prevent disease. New York (NY): Oxford University Press; 2010. Also available with modifications from URL: www.cdc.gov/genomics/resources/books/2009_HuGE/index.htm.