National Institutes of Health State-of-the-Science Conference Statement: Family History and Improving Health

Abstract

NIH Conferences15 December 2009National Institutes of Health State-of-the-Science Conference Statement: Family History and Improving HealthFREEAlfred O. Berg, MD, MPH, Macaran A. Baird, MD, MS, Jeffrey R. Botkin, MD, MPH, Deborah A. Driscoll, MD, Paul A. Fishman, PhD, Peter D. Guarino, PhD, MPH, Robert A. Hiatt, MD, PhD, Gail P. Jarvik, MD, PhD, Sandra Millon-Underwood, PhD, RN, Thomas M. Morgan, MD, John J. Mulvihill, MD, Toni I. Pollin, PhD, MS, Selma R. Schimmel, Michael Edward Stefanek, PhD, William M. Vollmer, PhD, and Janet K. Williams, PhD, RN, PNP*Alfred O. Berg, MD, MPHFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Macaran A. Baird, MD, MSFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Jeffrey R. Botkin, MD, MPHFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Deborah A. Driscoll, MDFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Paul A. Fishman, PhDFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Peter D. Guarino, PhD, MPHFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Robert A. Hiatt, MD, PhDFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Gail P. Jarvik, MD, PhDFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Sandra Millon-Underwood, PhD, RNFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Thomas M. Morgan, MDFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., John J. Mulvihill, MDFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Toni I. Pollin, PhD, MSFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Selma R. SchimmelFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., Michael Edward Stefanek, PhDFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., William M. Vollmer, PhDFrom University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California., and Janet K. Williams, PhD, RN, PNP*From University of Washington and Group Health Research Institute, Seattle, Washington; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Kaiser Permanente, Portland, Oregon; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California; University of Utah, Salt Lake City, Utah; University of Maryland School of Medicine, Baltimore, Maryland; Vanderbilt University, Nashville, Tennessee;University of Pennsylvania, Philadelphia, Pennsylvania; University of Iowa, Iowa City, Iowa; University of Minnesota, Minneapolis, Minnesota; American Cancer Society, Atlanta, Georgia; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; College of Nursing, Milwaukee, Wisconsin; and Vital Options International, Studio City, California.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0000605-200912150-00165 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail National Institutes of Health consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ); 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; 3) questions and statements from conference attendees during open discussion periods that are part of the public session; and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.Many common diseases have genetic, environmental, and lifestyle antecedents that family members share, and health care professionals in the United States have long used family history information as a risk assessment tool. In addition, most hereditary diseases have been elucidated through the study of families. A person's family history has the potential to capture information about shared factors that contribute to risk for common diseases, such as diabetes, stroke, cancer, and heart disease. Family history is also used routinely in many other ways, including its well-defined use in determining who might benefit from genetic testing and its use in the interpretation of genetic test results.The combination of these attributes makes the systematic collection of family history a potentially important step in personalizing health care. Several tools are in development to allow family history information to be effectively incorporated into health information technology systems, including electronic health records, personal health record systems, and family history risk assessment tools. Understanding the scientific foundation of family history is important if clinical decision aids (based on the information) are to be useful to clinicians and persons in typical practice settings and in improving clinical outcomes.Although the term family history is commonly used, it does not have a common definition—that is, various clinicians and patients understand it differently. Available family history questionnaires include information about a wide range of genetic, social, cultural, and environmental factors. Furthermore, family history questions may be embedded in complex risk assessment tools that incorporate many other demographic and health factors. Moreover, the definition of family varies when viewed from the perspectives of geneticists, generalist and specialist clinicians, family therapists, and members of some ethnic and cultural groups.The accuracy of patient-provided information is limited by a person's awareness, understanding, recollection, and willingness to disclose health issues of family members. The expected use of information from family history and the expected outcomes of acting on the information also vary depending on the clinical context. Important questions remain about the usefulness of family history information for disease prediction and improvement of individual health outcomes. Finally, the addition of new methods for systematically collecting family histories may alter the cost of care.Given the unprecedented proliferation of genomic information and the possibility of health care reform, it is imperative to clarify the role of the family history, its validity in the primary care setting, and its effect on individual and population health outcomes. Accordingly, the National Human Genome Research Institute and the Office of Medical Applications of Research of the National Institutes of Health convened a State-of-the-Science Conference to review the topic of family history and improving health. The Planning Committee narrowed the scope of the review to family history for common diseases as seen by clinicians in primary care, specifying a review to assess the available scientific evidence about the following 6 questions:1. What are the key elements of a family history in a primary care setting for the purposes of risk assessment for common diseases?2. What is the accuracy of the family history, and under what conditions does the accuracy vary?3. What is the direct evidence that getting a family history will improve health outcomes for the patient or family?4. What is the direct evidence that getting a family history will result in adverse outcomes for the patient or family?5. What are the factors that encourage or discourage obtaining and using a family history?6. What are future research directions for assessing the value of family history for common diseases in the primary care setting?The questions defined the scope of the review, which was further limited by the Technical Expert Panel in collaboration with the McMaster Evidence-based Practice Center. Inclusion criteria were common diseases, primary care population, and clinical outcomes recorded for individual patients rather than a group of patients. The evidence-based practice center further limited the review to include only studies published in English since 1995 that also reported quantitative data. For the questions reporting clinical outcomes, only controlled interventional trials were included. Consequently, it is important to emphasize that the review covers only a small portion of the evidence that might generally link family history to improved health.1. What Are the Key Elements of a Family History in a Primary Care Setting for the Purposes of Risk Assessment for Common Diseases?Critical to consideration of the value of family history in the assessment of the risk for common diseases is clarifying the key elements to establish in a primary care setting. An important limitation of a detailed ascertainment of family history is the brief length of a typical primary care visit. The standard against which this assessment can be made is the comprehensive, 3-generation pedigree used in medical genetics, counseling, and research settings.Key elements considered by the evidence report were 1) the number of affected relatives, 2) sex, 3) the degree of relationship (first- or second-degree relative), 4) age at onset, 5) ancestry (ethnicity or region of origin), and 6) lineage (maternal vs. paternal relatives). Other elements of family history were not considered in this review, such as consanguinity (blood relatives) and adoption status, as well as broader patterns of inheritance that are derived from a detailed and more time-consuming family history taken by a genetic counselor or medical geneticist. In addition, other elements not considered were the effect of environmental, social, and cultural factors that may influence the incidence and outcomes of common diseases and the role that family histories may have in establishing trust and good communication between the individual and clinician.What We KnowThe evidence report focused on several common medical conditions—asthma and allergies (atopic disease), diabetes, major depression and mood disorders, stroke, and cardiovascular or heart disease—and 5 common types of cancer (breast, ovarian, colorectal, prostate, and lung). It expressed its findings in terms of the sensitivity and specificity of selected family history elements for identifying persons with these conditions. The 59 studies included in the review were either 1) longitudinal in design and focused on the development (incidence) of disease, sometimes reporting more than 20 years of follow-up, or 2) cross-sectional in design and, hence, focused on the association with existing (prevalent) disease.The term sensitivity, as used in this context, refers to the probability that an affected person (someone with disease) will have a positive family history for the factor in question, whereas specificity refers to the probability that an unaffected person will have a negative family history. Although we would like both sensitivity and specificity to be as large as possible (that is, equal 1), in practice, the 2 measures tend to move in opposite directions. Thus, an increase in sensitivity is accompanied by a decrease in specificity and vice versa. The choice of emphasizing sensitivity or specificity depends on the cost or value of each option.The evidence report examined additional measures, such as the predictive value, relative risk, and odds ratio of a positive family history. For a particular aspect of family history (for example, having an affected first-degree relative), a high positive predictive value would exist if persons with such a history have a high probability of also having (or developing) disease, and a high odds ratio or relative risk would exist if those with a family history had or developed the disease with greater frequency than those without a family history. Relative risk, odds ratio, and predictive value all vary, not only with the sensitivity and specificity of the reported family history, but also with the prevalence of a disease in the population. For a given sensitivity and specificity, positive predictive value increases as the prevalence of disease increases. By contrast, the ability of a positive family history to predict disease can be very low, despite high sensitivity and specificity, if the disease reported occurs with very low frequency in the population.The most common family history methods covered in the evidence report were simple assessments of either any family history of a condition or history in a first-degree relative. Other aspects of family history for which information was available include family history in more distant relatives, lineage (maternal or paternal), age of onset in affected relatives, and sex of the affected relative. The evidence report provided little support to differentiate among these various measures. For almost all of the conditions for which data are available, sensitivities and positive predictive values were low (typically <25% for sensitivity and <10% for predictive value). Exceptions were for atopic diseases, mood disorders, and major depression, in which sensitivities were closer to 50% or more and predictive values ranged from 25% to 50%. Specificities, by contrast, tended to be very high (typical range, 90% to 98%). Atopic conditions and mental illnesses were again exceptions, with specificities ranging from 50% to 75%. Cross-sectional data generated somewhat higher sensitivities than longitudinal data. However, as stated in the evidence report, the literature supported the conclusion that family history, as currently measured in isolation, is neither a sensitive nor a highly predictive measure of common disease. Because most of the reported evidence was for recall of disease in a first-degree relative (and rarely for a second-degree relative, age of onset, and lineage) and many data were derived from research studies in a non–primary care setting, little evidence exists to help differentiate the key elements of a family history in a primary care setting.What We Need to LearnAlthough tools are being developed, we need evidence about where and how to collect family history systematically and how best to use this information in primary care. Furthermore, it is not clear that sensitivity, specificity, and predictive values are the best or are even appropriate measures to judge the relative value of key elements. Rather, approaches using relative risk and excess attributable risk for individual key elements compared with other elements (for example, presence of disease in a first-degree relative) and multivariable models should be explored. Beyond the key elements examined in the current evidence report, understanding the value of nongenetic elements included in a family history, such as environmental, social, and cultural aspects, is needed. These elements may vary in importance and influence in different racial, ethnic, cultural, and socioeconomic groups. Little is known about the ways in which electronic health records, modular software added to electronic health records, and other information technologies may affect the standardized collection of family history.2. What Is the Accuracy of the Family History, and Under What Conditions Does the Accuracy Vary?The accuracy of reported family history information can be viewed from the perspective of decision theory. We wish to know the true disease history of a person, but what we observe is a proxy's report of the person's disease history, and we do not know the accuracy of the information. As with the review for question 1, the evidence report presented data in terms of sensitivity and specificity. The only difference is that, for this question, sensitivity refers to the probability that an affected family member will be correctly identified as such, whereas specificity refers to the probability that an unaffected family member is correctly identified as disease-free.What We KnowUnlike the traditional decision-theory framework in which the "test criterion" is a well-defined measure with stable characteristics, the properties of reported family history are likely to vary from informant to informant and be related to personal factors, such as age, sex, cultural background, education, level of cognitive functioning, and whether the person who provided the information is adopted. Additional determinants of accuracy include the condition being reported (for example, breast cancer vs. depression) and how closely related the informant is to the person whose information is being provided (for example, a brother, sister, or other first-degree relative vs. a third cousin). If a person is cognitively impaired, a spouse or other surrogate, who may be less knowledgeable about the person's family history, may need to provide such information. Finally, the context in which family history is obtained may be important. For instance, parents may not wish to discuss certain issues in front of their children.The evidence report identified 35 studies that met the eligibility criteria for the review. Of these, 16 reported on the accuracy of family history of cancer, 11 on family history of mental health conditions, and 8 on other conditions. Many important conditions were not represented. In addition, an expert speaker report included 2 studies on the accuracy of cardiovascular disease history that the evidence report did not include.For those diseases included in the evidence report, specificity was generally high (90% to 95%), whereas sensitivity was lower and generally much more variable. The evidence report shows that the sensitivity for reports of various types of cancer ranged from 33% to 95%, whereas the sensitivity of mental health conditions ranged from 6% to 82%. In other words, persons more accurately report the absence of disease than the presence of disease in family members. Much less evidence exists for other conditions, such as autoimmune disease and substance abuse, and for relatives other than first-degree relatives.The lower accuracy for family histories of mental health disord