A
Methodology: Data Collection and Analysis

INTRODUCTION

The committee reviewed a broad array of information while considering the issues associated with assessing the impact on health of interactions among social, behavioral, physiological, and genetic factors. Sources of information included primary scientific literature in sociology, psychology, genetics, gene-environment interactions, and public health; books; scientific reviews; news articles; presentations from researchers, and representatives from the sponsor. Compilations of this background material commenced in December of 2004 and ended in February of 2006, shortly after the committee held its final meeting.

To answer questions that were posed to the committee in the statement of task, members of the committee relied on their own areas of expertise supplemented by various methods of information gathering that are described in more detail below.

Literature Review

The committee and Institute of Medicine (IOM) staff used an extensive online bibliographic search to compile a reference database of peer-reviewed literature relevant to the topic of the impact of interactions among social, behavioral, physiological, and genetic factors on health. The online bibliographic search was conducted using relevant databases (Box A-1) that included EMBASE, LexisNexis, Medline, PsychINFO, Science Direct, and



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A Methodology: Data Collection and Analysis INTRODUCTION The committee reviewed a broad array of information while consider- ing the issues associated with assessing the impact on health of interactions among social, behavioral, physiological, and genetic factors. Sources of information included primary scientific literature in sociology, psychology, genetics, gene-environment interactions, and public health; books; scientific reviews; news articles; presentations from researchers, and representatives from the sponsor. Compilations of this background material commenced in December of 2004 and ended in February of 2006, shortly after the com- mittee held its final meeting. To answer questions that were posed to the committee in the statement of task, members of the committee relied on their own areas of expertise supplemented by various methods of information gathering that are de- scribed in more detail below. Literature Review The committee and Institute of Medicine (IOM) staff used an extensive online bibliographic search to compile a reference database of peer- reviewed literature relevant to the topic of the impact of interactions among social, behavioral, physiological, and genetic factors on health. The online bibliographic search was conducted using relevant databases (Box A-1) that included EMBASE, LexisNexis, Medline, PsychINFO, Science Direct, and 223

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224 GENES, BEHAVIOR, AND THE SOCIAL ENVIRONMENT BOX A-1 Online Databases EMBASE (Excerpta Medica) database is a major biomedical and pharmaceutical containing more than 9 million records from 1974 to the present from over 4,000 journals; approximately 450,000 records are added annually. More than 80 per- cent of recent records contain full author abstracts. This bibliographic database indexes international journals in the following fields: drug research, pharmacology, pharmaceutics, toxicology, clinical and experimental human medicine, health pol- icy and management, public health, occupational health, environmental health, drug dependence and abuse, psychiatry, forensic medicine, and biomedical engi- neering/instrumentation. EMBASE is produced by Elsevier Science. LexisNexis provides access to full-text information from more than 5,600 sources, including national and regional newspapers, wire services, broadcast transcripts, international news, and non-English-language sources; U.S. federal and state case law, codes, regulations, legal news, law reviews, and international legal informa- tion; and business news journals, company financial information, Securities and Exchange Commission filings and reports, and industry and market news. It is produced by Reed Elsevier, Inc. MEDLINE is the U.S. National Library of Medicine’s premier bibliographic data- base, containing citations from the mid-1960s to the present and covering the fields of medicine, nursing, dentistry, veterinary medicine, the health care system, and the preclinical sciences. PubMed provides online access to more than 12 million MEDLINE citations. MEDLINE contains bibliographic citations and author abstracts from more than 4,600 biomedical journals published in the United States and 70 other countries. PubMed includes links to many sites providing full-text articles and other related resources. This database can be accessed at www. ncbi.nlm.nih.gov/PubMed. Sociological Abstracts. This online search was carried out throughout the entire course of the study. To begin the process of identifying peer-reviewed literature, the IOM staff conducted a general bibliographic search on topics that were relevant to interactions among genes and the social environment, and behavioral and physiological factors. IOM staff then categorized these references ac- cording to their subject matter and developed reference lists of key citations that were provided to the committee for review. After discussing the refer- ence lists with the committee, areas in which additional information was needed were determined. As the study progressed, searches of peer-reviewed literature continued regularly. Additional references were identified by reviewing the reference lists of major primary literature, key reports, relevant websites, and text-

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225 APPENDIX A PsycINFO is a bibliographic database of psychological literature with journal cov- erage from the 1800s to the present and book coverage from 1987 to the present. It contains more than 1,900,000 records, including citations and summaries of journal articles, book chapters, books, and technical reports, as well as citations to dissertations, all in the field of psychology and psychological aspects of related disciplines. Journal coverage includes full-text article links to 42 American Psycho- logical Association journals including peer-reviewed international journals. PsycINFO is produced by the American Psychological Association. Science Direct is a full-text journal database that indexes more than 1,800 scien- tific, technical, and medical peer-reviewed journals and contains more than 59 million abstracts and more than two million full-text scientific journal articles. Sub- ject coverage includes biological sciences; business management and account- ing; computer science; earth and planetary sciences; engineering and technology; environmental science; materials science; mathematics; medicine; physics and astronomy; psychology; and social science. Sociological Abstracts indexes the international literature in sociology and relat- ed disciplines in the social and behavioral sciences from 1963 to the present. This bibliographic database contains citations (from 1963) and abstracts (only after 1974) of journal articles, dissertations, conference reports, books, book chapters, and reviews of books, films, and software. Approximately 1,700 journals and 900 other serials published in the United States and other countries in more than 30 languages are screened yearly and added to the database bimonthly. The Socio- logical Abstracts database contained approximately 600,000 records in 2003. A limited number of full-text references are available. Sociological Abstracts is pre- pared by Cambridge Scientific Abstracts. books. Throughout the process, committee members, workshop presenters, and IOM staff supplied references and suggested key terms and authors relevant to the study. The IOM staff maintained a searchable database that was categorized to allow searches by keyword, type of literature (e.g., journal article), date, or other criteria. Reference lists of articles obtained were regularly updated and provided to the committee and consultants, who requested full text of the journal articles and other resources as needed for their information and analysis. After many months of reviewing the rapidly expanding literature avail- able, the final count of articles was more than one thousand. Two-thirds of the articles obtained were published after the year 2000, a reflection of the fact that interest in studying the impact of interactions among social, be- havioral, physiological, and genetic factors on health continues to increase.

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226 GENES, BEHAVIOR, AND THE SOCIAL ENVIRONMENT Commissioned Papers In the statement of task the committee was asked to “develop case studies (e.g., obesity, stress, smoking) that will: demonstrate how the inter- actions of the social environment and genetics affect health outcomes; illus- trate the methodological issues involved in measuring the interactions; elu- cidate the research gaps; point to key areas necessary for integrating social, behavioral, and genetic research; and suggest mechanisms for overcoming barriers.” The committee chose to address this task by obtaining commis- sioned papers on sickle cell disease and obesity that would focus on the points illustrated in the statement of task. Myles S. Faith, Ph.D., and Tanya V.E. Kral, Ph.D., from the University of Pennsylvania School of Medicine, were identified as the foremost experts with the specialized knowledge necessary to write the commissioned paper on obesity. Dr. Faith and Dr. Kral provided the committee with a paper entitled “Social Environmental and Genetic Influences on Obesity and Obesit-Promoting Behaviors: Fos- tering Research Integration,” which can be found in Appendix C. The committee identified Robert J. Thompson, Jr., Ph.D., from Duke Univer- sity, as having the necessary knowledge and expertise to prepare the paper on sickle cell disease. He provided the committee with a paper entitled “The Interaction of Social, Behavioral, and Genetic Factors in Sickle Cell Dis- ease,” which can be found in Appendix D. The committee also determined the need for a detailed analysis of genetic interactions and the current state of the science in this area. Sharon Schwartz, Ph.D., at Columbia University’s Mailman School of Public Health, was asked to write this paper and provided the committee with a paper titled “Modern Epidemiologic Approaches to Interaction: Applica- tions to the Study of Genetic Interactions,” which can be found in Appen- dix E. Steve Cole, Ph.D., at the University of California at Los Angeles David Geffen School of Medicine, also provided a commissioned paper on immunology that was designed to increase the committee’s understanding of the impact of social and genetic variation on immune function and the state of the science of this area. Information from all four commissioned papers was used to invigorate committee deliberations and enhance the quality of the report. Public Workshops The committee held a total of five meetings over the course of the project. The purpose of these meetings was to address the study charge, review the data collected, and develop the report and recommendations. The first three meetings held by the committee included data-gathering

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227 APPENDIX A BOX A-2 Open Agenda for Meeting 1: March 28-29, 2005 Institute of Medicine Committee on Assessing Interactions Among Social, Behavioral, and Genetic Factors in Health 500 5th St., NW Washington, D.C. 20001 Open Session: March 28, 2005 10:00 Welcome and Introduction Dan G. Blazer, M.D., Committee Chair 10:15 Sponsor Presentation of Charge Ronald Abeles, Ph.D., OBSSR 10:45 Discussion and Clarification of Charge sessions, which were open to the public. These were held on March 28-29, 2005, June 16-17, 2005, and September 29-30, 2005. In preparation for the data-gathering sessions, the committee discussed areas in which there were gaps in the knowledge of committee members. Once the gaps were identified, the committee developed a set of questions that needed to be answered in order for the committee to adequately ad- dress the statement of task. The committee then identified potential speak- ers with the appropriate level of expertise to address the questions and invited them to participate in open session workshops. The first committee meeting, held March 28-29, 2005, in Washington, D.C. (Box A-2), included a presentation of the charge to the committee by Ronald Abeles of the Office of Behavioral and Social Sciences Research (OBSSR) and an open discussion of the statement of task with representa- tives from each of the sponsors from the National Institutes of Health, including Ronald Abeles and Deborah Olster from OBSSR, Colleen McBride from the National Human Genome Research Institute, and Brian Pike from the National Institute of General Medical Sciences. The second committee meeting, held June 16-17, 2005, in Washington, D.C. (Box A-3), was the first of the two open data-gathering sessions. During this meeting, the committee heard presentations from seven speak- ers who provided overviews of social variables, genetics variables, gene

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228 GENES, BEHAVIOR, AND THE SOCIAL ENVIRONMENT BOX A-3 Open Agenda for Meeting 2: June 16-17, 2005 Institute of Medicine Committee on Assessing Interactions Among Social, Behavioral, and Genetic Factors in Health Washington Terrace Hotel 1515 Rhode Island Ave., NW Washington, D.C. 20005 Director’s Room (second floor) Open Session: June 16, 2005 9:30 Welcome and Introductions Dan Blazer M.D., Ph.D. Committee Chair J.P. Gibbons Professor of Psychiatry Duke University Medical Center 9:45 Overview of Social Variables and Their Measurement Ana Diez Roux, Ph.D. Associate Professor of Epidemiology Associate Director of the Center for Social Epidemiology and Population Health University of Michigan School of Public Health 10:05 Conceptualizing Social Variables to Facilitate and Promote Gene/Environment Research Eileen Crimmins, Ph.D. Edna M. Jones Professor of Gerontology and Sociology University of Southern California 10:25 Discussion 11:00 Overview of Genetic Variables and Their Measurement Sharon Kardia, Ph.D. Director, Public Health Genetic Programs Associate Professor, Department of Epidemiology University of Michigan School of Public Health

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229 APPENDIX A 11:20 Discussion 11:45 LUNCH 1:00-2:45 PANEL ON EPIGENETICS 1:00 Gene Expression over Time Ming D. Li, Ph.D. Associate Professor/START Center Genetic Professorship Head, Program in Genomics and Bioinformatics on Drug Addiction University of Texas Health Science Center at San Antonio 1:20 Epigenetic Phenomenon: How to Approach Mechanisms by Which Social Variables Influence Gene Expression Arthur Beaudet, M.D. Chair, Department of Molecular and Human Genetics Baylor College of Medicine 1:40 Genetics of Ethnic Populations Sharon Kardia, Ph.D. Director, Public Health Genetic Programs Associate Professor, Department of Epidemiology University of Michigan School of Public Health 2:00 Implications of Genetics of Ethnic Populations for Common Disease Keith Whitfield, Ph.D. Associate Professor of Biobehavioral Health Pennsylvania State University 2:20 Animal Models John Sheridan, Ph.D. Professor, College of Medicine and Public Health Associate Director, Institute for Behavioral Medicine Research Ohio State University 2:45 Discussion 3:30 Workshop Adjourns

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230 GENES, BEHAVIOR, AND THE SOCIAL ENVIRONMENT BOX A-4 Open Agenda for Meeting 3: September 29-30, 2005 Institute of Medicine Committee on Assessing Interactions Among Social, Behavioral, and Genetic Factors in Health Keck Building, Room 100 500 5th St., NW Washington, D.C. 20001 Open Session: September 29, 2005 9:00 Welcome and Introductions Dan Blazer, M.D., Ph.D. Professor of Psychiatry Duke University Committee Chair 9:15 Cultural Influences on Health Margaret Lock, Ph.D. Professor in Social Studies in Medicine McGill University 9:45 Discussion 10:00 Effects of Psychological Stress on Health Sheldon Cohen, Ph.D. Professor of Psychology Carnegie Mellon University 10:30 Discussion 11:00 Gene-Environment Interactions: Definitions and Study Design Ruth Ottman, Ph.D. Professor of Epidemiology Columbia University 11:30 Discussion 12:00 Workshop Adjourns

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231 APPENDIX A expression over time, epigenetics, genetics of ethnic populations, and ani- mal models. The third committee meeting, held on September 29-30, 2005, in Wash- ington, D.C. (Box A-4), was the second main data-gathering session open to the public. During this meeting, the committee heard presentations from three speakers who provided overviews of cultural influences on health, the effects of psychological stress on health, and gene-environment interac- tions. The remaining two committee meetings were closed to the public in order to permit committee deliberation and report writing. They were held in November of 2005 and January of 2006.