Paula W. Yoon

The continuum of translation research in genomic medicine: how can we accelerate the appropriate integration of human genome discoveries into health care and disease prevention?

Advances in genomics have led to mounting expectations in regard to their impact on health care and disease prevention. In light of this fact, a comprehensive research agenda is needed to move human genome discoveries into health practice in a way that maximizes health benefits and minimizes harm to individuals and populations. We present a framework for the continuum of multidisciplinary translation research that builds on previous characterization efforts in genomics and other areas in health care and prevention. The continuum includes four phases of translation research that revolve around the development of evidence-based guidelines. Phase 1 translation (T1) research seeks to move a basic genome-based discovery into a candidate health application (e.g., genetic test/intervention). Phase 2 translation (T2) research assesses the value of a genomic application for health practice leading to the development of evidence-based guidelines. Phase 3 translation (T3) research attempts to move evidence-based guidelines into health practice, through delivery, dissemination, and diffusion research. Phase 4 translation (T4) research seeks to evaluate the “real world” health outcomes of a genomic application in practice. Because the development of evidence-based guidelines is a moving target, the types of translation research can overlap and provide feedback loops to allow integration of new knowledge. Although it is difficult to quantify how much of genomics research is T1, we estimate that no more than 3% of published research focuses on T2 and beyond. Indeed, evidence-based guidelines and T3 and T4 research currently are rare. With continued advances in genomic applications, however, the full continuum of translation research needs adequate support to realize the promise of genomics for human health.

Can family history be used as a tool for public health and preventive medicine

Most common chronic diseases are the result of complex interactions between multiple genetic variants and environmental factors. Despite significant advances in the last decade in the understanding of our genome, there are substantial limitations in epidemiological and analytic approaches to studying the effects of genetic determinants of common chronic diseases. Knowledge of genetic variation underlying disease susceptibility should improve our ability to diagnose, manage, and prevent these disorders. To date, however, DNA-based testing is limited for the most part to analysis of highly penetrant single gene disorders that account for approximately 5% of the total disease burden in the population.1, 2 It may be years before DNAbased tests are routinely applied to predict the onset of common diseases, their natural history, and response to therapy.

Family History in Public Health Practice: A Genomic Tool for Disease Prevention and Health Promotion*

Family history is a risk factor for many chronic diseases, including cancer, cardiovascular disease, and diabetes. Professional guidelines usually include family history to assess health risk, initiate interventions, and motivate behavioral changes. The advantages of family history over other genomic tools include a lower cost, greater acceptability, and a reflection of shared genetic and environmental factors. However, the utility of family history in public health has been poorly explored. To establish family history as a public health tool, it needs to be evaluated within the ACCE framework (analytical validity; clinical validity; clinical utility; and ethical, legal, and social issues). Currently, private and public organizations are developing tools to collect standardized family histories of many diseases. Their goal is to create family history tools that have decision support capabilities and are compatible with electronic health records. These advances will help realize the potential of family history as a public health tool.

Family History and Prevalence of Diabetes in the U.S. Population

OBJECTIVE—We sought to test the association between stratified levels of familial risk of diabetes and the prevalence of the disease in the U.S. population. RESEARCH DESIGN AND METHODS—This study includes 16,388 adults interviewed for the National Health and Nutrition Examination Survey between 1999 and 2004. Fasting glucose was available for a subsample of 6,004 participants. Familial risk of diabetes was classified as average, moderate, or high. The prevalence and the odds of having diabetes were estimated for each risk class after accounting for other risk factors. RESULTS—Overall, 69.8% of the U.S. adults were in the average, 22.7% in the moderate, and 7.5% in the high familial risk for diabetes. The crude prevalence of diabetes for each risk class was 5.9, 14.8, and 30%, respectively. The graded association between familial risk and prevalence of diabetes remained even after accounting for sex, race/ethnicity, age, BMI, hypertension, income, and education. Versus people in the average risk class, independently of other risk factors considered, the odds of having diabetes for people in the moderate and high familial risk categories were, respectively, 2.3 and 5.5 times higher. CONCLUSIONS—In the U.S. population, family history of diabetes has a significant, independent, and graded association with the prevalence of diabetes. This association not only highlights the importance of shared genes and environment in diabetes but also opens the possibility of formally adding family history to public health strategies aimed at detecting and preventing the disease.

Family history of type 2 diabetes: A population-based screening tool for prevention?

Purpose: To evaluate the use of self-reported family medical history as a potential screening tool to identify people at-risk for diabetes.Methods: The HealthStyles 2004 mail survey comprises 4345 US adults who completed a questionnaire to ascertain personal and family history of diabetes, perceived risk of diabetes, and practice of risk-reducing behaviors. Using number and type of affected relatives, respondents were ranked into three familial risk levels. Adjusted odds ratios (AORs) were obtained to evaluate associations between familial risk and prevalent diabetes, perceived risk of disease, and risk-reducing behaviors. Validity of family history as a screening tool was examined by calculating sensitivity, specificity, and positive and negative predictive values.Results: Compared to those of average risk, people with moderate and high familial risk of diabetes were more likely to report a diagnosis of diabetes (AOR: 3.6, 95% CI: 2.8, 4.7; OR: 7.6, 95% CI: 5.9, 9.8, respectively), a higher perceived risk of diabetes (AOR: 4.6, 95% CI: 3.7, 5.7; OR: 8.5, 95% CI: 6.6, 17.7, respectively), and making lifestyle changes to prevent diabetes (AOR: 2.2, 95% CI: 1.8, 2.7; OR: 4.5, 95% CI: 3.6, 5.6, respectively). A positive familial risk of diabetes identified 73% of all respondents with diabetes and correctly predicted prevalent diabetes in 21.5% of respondents.Conclusion: Family history of diabetes is not only a risk factor for the disease but is also positively associated with risk awareness and risk-reducing behaviors. It may provide a useful screening tool for detection and prevention of diabetes.

Familial risk for common diseases in primary care: the Family Healthware Impact Trial.

CONTEXT Family history is a risk factor for many common chronic diseases, yet it remains underutilized in primary care practice. BACKGROUND Family Healthware is a self-administered, web-based tool that assesses familial risk for CHD; stroke; diabetes; and colorectal, breast, and ovarian cancer, and provides a personalized prevention plan based on familial risk. The Family Healthware Impact Trial evaluated the tool. DESIGN In this cluster RCT, participants completed baseline and 6-month follow-up surveys. The intervention group used Family Healthware directly after the baseline survey. Controls used the tool after completing the follow-up survey. SETTING/PARTICIPANTS Patients aged 35-65 years with no known diagnosis of these six diseases were enrolled from 41 primary care practices. MAIN OUTCOME MEASURES The prevalence of family-history-based risk for coronary heart disease (CHD); stroke; diabetes; and colorectal, breast, and ovarian cancer was determined in a primary care population. RESULTS From 2005 to 2007, 3786 participants enrolled. Data analysis was undertaken from September 2007 to March 2008. Participants had a mean age of 50.6 years and were primarily white (91%) women (70%). Of the 3585 participants who completed the risk assessment tool, 82% had a strong or moderate familial risk for at least one of the diseases: CHD (strong=33%, moderate=26%); stroke (strong=15%, moderate=34%); diabetes (strong=11%, moderate=26%); colorectal cancer (strong=3%, moderate=11%); breast cancer (strong=10%, moderate=12%); and ovarian cancer (strong=4%, moderate=6%). Women had a significantly (p<0.04) higher familial risk than men for all diseases except colorectal and ovarian cancer. Overweight participants were significantly (p<or=0.02) more likely to have a strong family history for CHD, stroke, and diabetes. Older participants were significantly (p<or=0.02) more likely to report a strong family history for CHD and stroke as well as colorectal and breast cancer. CONCLUSIONS This self-administered, online tool delineated a substantial burden of family-history-based risk for these chronic diseases in an adult, primary care population. TRIAL REGISTRATION NCT00164658.

Using family history information to promote healthy lifestyles and prevent diseases; a discussion of the evidence.

BackgroundA family history, reflecting genetic susceptibility as well as shared environmental and behavioral factors, is an important risk factor for common chronic multifactorial diseases such as cardiovascular diseases, type 2 diabetes and many cancers.DiscussionThe purpose of the present paper is to discuss the evidence for the use of family history as a tool for primary prevention of common chronic diseases, in particular for tailored interventions aimed at promoting healthy lifestyles. The following questions are addressed: (1) What is the value of family history information as a determinant of personal disease risk?; (2)How can family history information be used to motivate at-risk individuals to adopt and maintain healthy lifestyles in order to prevent disease?; and (3) What additional studies are needed to assess the potential value of family history information as a tool to promote a healthy lifestyle?SummaryIn addition to risk assessment, family history information can be used to personalize health messages, which are potentially more effective in promoting healthy lifestyles than standardized health messages. More research is needed on the evidence for the effectiveness of such a tool.

Is family history a useful tool for detecting children at risk for diabetes and cardiovascular diseases? A public health perspective.

Several studies indicate that the risk for type 2 diabetes or cardiovascular disease is detectable in childhood, although these disorders may not emerge until adulthood. In addition, type 2 diabetes and cardiovascular disease seem to share risk factors, including obesity and dyslipidemia, and might even share etiology, which has important implications for screening and prevention strategies for both diseases. Primary prevention, in particular, has gained importance because the results of major randomized, controlled trials strongly suggest that, at least in high-risk adult groups, type 2 diabetes can be prevented or delayed. Furthermore, some intervention studies indicate that the risk factors for diabetes and cardiovascular disease can be reduced in children. A simple way to detect risk for either diabetes or cardiovascular disease is to examine the family history. Numerous studies have shown that adults who have 1 or more first- or second-degree relatives affected with diabetes or cardiovascular disease are at high risk of having or developing these diseases. Currently, there are no overall screening strategies recommended for either diabetes or cardiovascular disease among children and adolescents. The evidence is strong, however, that youth with a positive family history already show signs of increased risk for these conditions. Family history can be part of the approach to screening for children at risk of diabetes and cardiovascular disease and should be part of prevention campaigns aimed at reducing the burden of these diseases and their risk factors in children.

Familial risk assessment for early-onset coronary heart disease

Purpose: We examined the performance of a familial risk assessment method that stratifies risk for early-onset coronary heart disease by considering the number of relatives with coronary disease, degree of relationship, lineage, and age at diagnosis.Methods: By using data from the HealthStyles 2003 survey, we assessed the associations between familial risk and early-onset coronary heart disease, diabetes, hypercholesterolemia, hypertension, and obesity. By using area under the curve statistics, we evaluated the discriminatory ability of various risk assessment models.Results: Of 4035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years. After adjustment for demographics, strong and moderate risk were significantly associated with approximately a five- and twofold risk of early-onset coronary disease, respectively. After adjustment for demographics and personal history of cardiovascular disease, strong familial risk was also significantly associated with diabetes, hypercholesterolemia, hypertension, and obesity. A risk assessment model that included familial risk, demographics, and personal history of diabetes, hypercholesterolemia, hypertension, and obesity was most optimal with an area under the curve statistic of 87.2%Conclusions: Familial risk assessment can stratify risk for early-onset coronary heart disease. Several conditions associated with increased familial risk can be prevented. These results have important implications for risk assessment and risk-reducing interventions.

Expanding the definition of a positive family history for early-onset coronary heart disease

Purpose: Assessing familial risk for early-onset coronary heart disease (CHD) is typically limited to first-degree relatives with early-onset CHD. To evaluate the impact of additional family history, we examined the associations between various family history definitions and early-onset CHD.Methods: By using the national HealthStyles 2003 survey data, we assessed associations between self-reported family history and personal history of early-onset CHD (diagnosed at or before age 60 years), adjusting for demographics, hypercholesterolemia, hypertension, and obesity.Results: Of 4035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years; 4.4% had early-onset CHD. In addition to having at least one first-degree relative with early-onset CHD, other significant associations included having at least one first-degree relative with late-onset CHD, at least one second-degree relative with early-onset CHD, and two or more affected second-degree relatives regardless of age of onset of CHD. Early-onset stroke in at least one first-degree relative and, in women, having at least one first-degree relative with diabetes were also significantly associated with early-onset CHD.Conclusions: Family history beyond early-onset CHD in first-degree relatives is significantly associated with prevalent CHD diagnosed at or before age 60 years.