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.

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

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 according to their subject matter and developed reference lists of key citations that were provided to the committee for review. After discussing the reference 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-

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 available, 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, behavioral, physiological, and genetic factors on health continues to increase.

In the statement of task the committee was asked to “develop case studies (e.g., obesity, stress, smoking) that will: demonstrate how the interactions of the social environment and genetics affect health outcomes; illustrate the methodological issues involved in measuring the interactions; elucidate 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 commissioned 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: Fostering Research Integration,” which can be found in Appendix C. The committee identified Robert J. Thompson, Jr., Ph.D., from Duke University, 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 Disease,” 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: Applications to the Study of Genetic Interactions,” which can be found in Appendix 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.

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

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 address the statement of task. The committee then identified potential speakers 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 representatives 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 speakers who provided overviews of social variables, genetics variables, gene

expression over time, epigenetics, genetics of ethnic populations, and animal models.

The third committee meeting, held on September 29-30, 2005, in Washington, 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 interactions. 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.