Social and behavioral science priorities for genomic translation

This commentary discusses how the social/behavioral sciences and genomics might more effectively be integrated to advance treatments and interventions.

Abstract

This commentary highlights the essential role of the social and behavioral sciences for genomic translation, and discusses some priority research areas in this regard. The first area encompasses genetics of behavioral, social, and neurocognitive factors, and how integration of these relationships might impact the development of treatments and interventions. The second area includes the contributions that social and behavioral sciences make toward the informed translation of genomic developments. Further, there is a need for behavioral and social sciences to inform biomedical research for effective implementation. The third area speaks to the need for increased outreach and education efforts to improve the public’s genomic literacy such that individuals and communities can make informed health-related and societal (e.g., in legal or consumer settings) decisions. Finally, there is a need to prioritize representation of diverse communities in genomics research and equity of access to genomic technologies. Examples from National Institutes of Health-based intramural and extramural research programs and initiatives are used to discuss these points.

Implications

Practice: The social and behavioral sciences have a key role to play in translation of genomic discoveries into the clinic, families, and communities.

Policy: Optimal integration of genomic information into health care or public health practice will be enhanced through an evidence base grounded in social and behavioral sciences theory using novel methods and sensitive measures.

Research: Social and behavioral sciences research priorities for genomic translation include genomic discovery of behavioral, social, and neurocognitive factors; social and behavioral sciences informed translation of genomic discoveries; programs aimed at improving genomic literacy for both providers and the general public; and consideration of diverse communities in these efforts.

INTRODUCTION

In 2003, the Human Genome Project was completed amid great excitement for the future translation of genomic discoveries [1]. Indeed, we have seen significant increases in our understanding of genomic contributors to health and disease. Some of this discovery reflects increased understanding of the biological mechanisms that underlie disease; other advances identify gene–environment or gene–behavior interaction-based influences on health. In both cases, these genomic discoveries have the potential for broad impact on public health and wellbeing. Within this context of scientific advancement, the unique role that the social and behavioral sciences are poised to play toward the goals of genomic translation cannot be overstated.

There are several perspectives to consider when thinking about how social and behavioral sciences fit relative to the translation of genetic (i.e., single genes and their roles in inheritance) and genomic (i.e., all of an individual’s genes, their interaction with each other, and their interactions with the environment) discoveries [2]. First, there is a large body of research that examines genetic factors that influence or are influenced by behavior and social phenomena that, in turn, can impact health outcomes [3, 4]. Arguably, the goal for this research is to better understand and improve health. As such, it is imperative for the scientific community to consider how findings from this basic research translate to adoptable treatments and interventions. Another, perhaps more immediately feasible perspective, is the application of social and behavioral sciences research to inform translation of genetic and genomic findings into effective clinical treatments and public health interventions. To do so effectively, social and behavioral research has an important role to play in preparing both the healthcare sector and broader communities to understand and apply genetic and genomic information such that they can make informed medical and societal decisions related to genomic translation. Finally, investigating ways to promote optimal dissemination and reach of genomic translation will require special attention to the social factors and behavioral tendencies that underlie the potential for health inequities.

In all of these research agendas, the social and behavioral sciences are inexorably tied to achieving successful genomic translation within the clinic and into communities. For example, clinical translation relies upon patient–provider communications to convey information about genomic factors in health and to arrive at decisions about whether and how to use genomic technologies. These conversations are necessarily shaped by social and psychological forces such as patient and provider attributes, interpersonal characteristics, and the messages used within the interaction. In addition, optimal translation often relies upon patients sharing what they learn in the clinic with their family members, which is dependent upon family dynamics and the functioning of family systems. Importantly, consideration of the potential for genomics to exacerbate or reduce health disparities is a common thread running through all translational efforts, which must take into account interpersonal behavior as well as broader social structures, both of which fall squarely within the social and behavioral science domains. In this commentary, we highlight the importance of the behavioral and social sciences in the translation of genomic research for clinical and public health utility through the lens of recent National Institutes of Health (NIH)-funded programs, and articulate key social and behavioral sciences priorities and opportunities in the clinical and community translation of genomics to come.

PRIORITY 1: GENETICS OF BEHAVIORAL, SOCIAL, AND NEUROCOGNITIVE FACTORS

There is a long history of exploring the genetics of behavior, an endeavor in which social and behavioral scientists have taken a lead role. Doing so has increased understanding of the trajectories of human development, of how the environment can impact development through gene–environment interactions and correlations, and, in cases of behavioral disorders and syndromes, has helped to elucidate pathways that have assisted in emergent therapies.

Here, the NIH has taken an active role, initiating several trans-NIH initiatives in the interest of identifying basic mechanisms of health and disease. Critically, these initiatives move beyond exploration of biological factors, and emphasize the integration of genetics with behavioral, social, and other disciplines. Four initiatives (The Environmental Influences on Child Health Outcomes [ECHO], The Adolescent Brain Cognitive Development Study [ABCD], The Brain Research through Advancing Innovative Neurotechnologies [BRAIN], All of Us; see inset Box 1) have the potential for generating revolutionary basic findings that will have a substantial impact on how we understand the interplay between genetics, behavior, and social factors as they jointly influence health. Findings that come out of these initiatives also have the potential to fuel work on translational research. For example, ECHO is a monumental scientific undertaking that has the potential to simultaneously examine how a broad range of environmental factors, including behavioral and social factors, might individually and synergistically influence trajectories of child health outcomes while taking genetic information into account. Likewise, ABCD is currently in the field collecting extensive amounts of basic data, including genetic data, on children’s brains with the intent of better understanding developmental trajectories with the express purpose of fueling the development of prevention and intervention efforts. Through the use of a broad range of innovative technology, including genetic and genomic advances, BRAIN will produce resources providing basic information about the brain that have long been missing for researchers interested in developing a broad range of tools and resources that will allow for more applied, translational research to unfold. Finally, the primary goal of All of Us is to catalyze and revolutionize precision medicine through the collection of basic data that will allow for a better understanding of individual differences in key disease areas. What is particularly revolutionary about each of these projects is the broad involvement of the research community in the planning and implementation of each initiative, the inclusion of behavioral, social, and biomedical sciences in the data collection and assessment strategies, as well as the subsequent availability of data and resources for use by the scientific community.

Box 1 | NIH Initiatives at the Intersection of Genomics and the Social and Behavioral Sciences

ECHO: The Environmental Influences on Child Health Outcomes (ECHO) is a relatively new NIH initiative focused on understanding the effects of a broad range of environmental exposures on child health and development. These include multiple measures such as familial relationships and home environment along with child social roles and health behaviors. This, along with the collection of biological samples, will allow for the analysis of genetic influences on child development and health. ECHO will capitalize on existing cohorts to focus on four key pediatric outcomes (upper and lower airway, obesity, pre-, peri-, and postnatal outcomes, and neurodevelopment). Core data elements will be collected in the prospective data collection portion of the initiative. More detailed information can be found here: https://www.nih.gov/echo.

ABCD: The Adolescent Brain Cognitive Development Study (ABCD) is the largest long-term study of brain development and child health in the United States. Twenty-one research sites across the country will recruit approximately 10,000 children between 9 and 10 years of age and follow them into early adulthood. The goal is to integrate structural and functional brain imaging with genetic, neuropsychological, behavioral, and other health assessments to better understand factors that enhance or disrupt life trajectories. Relevant to social and behavioral sciences, the interaction of factors such as sleep behaviors, internet use, and social involvement with child brain development and overall health will be explored. Data collected from this study will be made available to qualified researchers. https://abcdstudy.org/index.html

BRAIN: The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has partners across the U.S. government, and intends to revolutionize the understanding of the human brain by accelerating the development and application of innovative technologies. Novel techniques will allow for brain-behavior quantification with enhanced temporal resolutions. This new knowledge will provide new opportunities for researchers seeking to treat, cure, and prevent brain disorders. https://www.braininitiative.nih.gov

All of Us: The All of Us Research Program (formerly PMI: Precision Medicine Initiative) will extend precision medicine to all diseases through the creation of a national research cohort of 1 million or more U.S. participants. This is a participant-engaged, data-driven effort that will integrate a broad range of scientific areas including human biology, behavior, genetics, environment, data science, and computation. Precision medicine considers individual differences in genes and environment and large-scale initiatives such as this will accelerate individualized treatments for a wide range of diseases both common and uncommon. Data sharing is an integral component and researchers will be able to obtain data to study a range of health conditions. https://allofus.nih.gov

Such efforts will provide the basis for explicating the genetic, biological, behavioral and social mechanisms that impact health, and importantly, given the collaborative nature of these initiatives, there is promise for identifying how these domains might interact to shape health and disease over the lifecourse. Such efforts will provide necessary information for tailoring interventions towards those who might benefit most.

Issues of genomic influence on neurocognitive and behavioral factors are being tackled in the NIH Intramural Research Program (IRP) as well. For example, distinct neurodevelopmental trajectories associated with the persistence of attention deficit-hyperactivity disorder (ADHD) into adulthood have been identified [5, 6]. Recent efforts suggest that aspects of these neurodevelopmental trajectories are highly heritable, and that there are genetic and epigenetic factors associated with the neuroanatomical anomalies associated with ADHD [7, 8]. This work will inform development of both diagnostic tools to identify those at most risk of persistent ADHD and early interventions that target neural plasticity to normalize neurodevelopment which may promote ADHD remission.

These existing NIH-based initiatives and projects will bring us quite some distance in elucidating genetic factors relevant to behavioral, social, and neurocognitive mechanisms of health and disease. Ideally, however, these ideas would achieve broader reach in the research community. Given the potential for behavioral intervention to impact biological mechanisms such as genetic expression, and for genomic factors to modulate responses to one’s social environment, we envision a broadening of the definition of environmental exposures within basic science research. Consider, for example, the context of stress research, where stressors may represent exposures from the natural environment, limited access to resources within communities, or lack of support through interpersonal ties. Recent studies suggest several genetic variants are important in determining susceptibility and resilience to developing mental and physical health problems under socioenvironmental stress [4, 9]. Future research that examines how such environmental exposures are embodied through microbial, inflammatory, or epigenetic processes has important implications for therapeutic intervention [10, 11]. As well, given that such biological responses represent more proximal outcomes that can be influenced by behavior, these responses may provide more sensitive measures of intervention effectiveness. Indeed, the social and behavioral sciences have much to contribute to the identification and understanding of these broader environmental variables and the role they play in influencing health. ECHO and ABCD, in particular, have embraced a broader definition of the environment (including multiple aspects of physical and social environments) at the basic data collection and analytic stages, which bodes well for a more complete understanding of how to integrate different elements of the environment into future intervention and treatment efforts.

PRIORITY 2: BEHAVIORAL AND SOCIAL SCIENCE-INFORMED TRANSLATION OF GENOMIC ADVANCES

Optimal translation of genomic discoveries will require focus on the clinic, families, and communities. As such, basic social and bjehavioral sciences research identifying influence of relevant factors on the use of genomics is needed to inform both clinical therapies and behavioral interventions. In addition, clinical translation involving genetic or genomic risk assessments used to guide prevention decisions, early detection efforts, and treatment [12, 13], will need to be developed with the expectation that this information can move beyond the clinic to families and communities. Key priorities in this area include expanding our understanding of how social and behavioral social sciences theory can improve implementation science, development of novel methods for testing translational hypotheses, and identifying more sensitive measures for risk evaluation or intervention outcomes relative to genomic translation.

Currently, the predominant translational approach is focused on the provision of genetic risk assessments for influencing health behavior. There is substantial evidence regarding the clinical and economic utility of genetic testing among persons affected by hereditary cancer syndromes for which there are clear medical benefits [14–17]. However, there has been debate as to the utility of genetic risk information for complex conditions to motivate behavior change [18, 19]. There may be little reason to believe that genetic information should change behavior, particularly since the predictive ability of any common variant we can provide for people is very weak. However, communication about the holistic concept of genomics, family-based risk, as well as the potential risk profiles associated with future genomic technologies may be able to accomplish much more with respect to behavior change. In addition, genomic information alone may not be sufficient to motivate behavior change, suggesting an important place for social and behavioral sciences theory to inform intervention practices.

Indeed, grounded in interdependence theory, work within the NIH IRP has shown that family health history may represent a genomic tool that is particularly effective in motivating behavior change through interpersonal support mechanisms. For example, family history-based risk information may activate protection motivations in parents towards their children, resulting in shifts towards more healthful child feeding behavior [20], encouragement of their child’s physical activity, and coengagement in physical activities with their child [21]. Similarly, family history-based risk can impact spouses’ behavior; for example, recent work showed that wives improved their lifestyle in response to their spouses’ increased disease risk assessment, but not their own increased risk assessment and, for both husbands and wives, encouraging their at-risk spouse to maintain a healthy weight was important in sustaining their own behavior change (see paper in this special issue) [22]. Thus, behavior change interventions that capitalize on interpersonal mechanisms within the family through inherited family risk information may be particularly salient.

In addition to work focusing on leveraging notions of shared, inherited risk in the family, communication about potential future risk profiles that are envisioned given advances in genomic technology may also result in more effective behavioral change. However, assessing the influence of these interventions and optimizing communication approaches for delivering them is not possible in current clinical environments. One approach that has been used in the NIH IRP is the application of virtual reality-based simulation tools to investigate patient reactions to potential genomic risk profiles, and assess how patient and provider attributes, when considered in the context of genomic medicine, impact the clinical experience and clinical decision-making. For example, providing genomic information in the context of obesity, a complex condition, has been found to reduce clinician stereotyping of and increase eye contact with a patient with obesity, and to reduce patients’ perceptions of blame and stigmatization by the physician [23–25]. In addition, through these simulated interactions, research has shown that racial concordance between providers and patients was associated with more engagement in the clinical interaction, and appears to improve the accuracy of patients’ genomics-oriented disease risk perception following the clinical encounter [26, 27]. As such, characteristics of the patient–provider encounter may be important to consider when crafting communication approaches in genomic medicine translation contexts.

Finally, in addition to innovation in research methods, there is also a need to consider innovation in risk assessment approaches and measurement of intervention outcomes. Recent work in the NIH IRP has taken up this challenge on several fronts. For example, one research program shows how a social network framework and psychometric principles can result in more sensitive family health history-based risk assessments by pooling family history information obtained from multiple informants who are biologically related [28]. If clinicians integrate the gold-standard three-generation pedigree into patient electronic health records (EHRs) [29], this multi-informant perspective could be easily implemented by linking EHR family histories across related individuals [30], with risk algorithms running in the background to protect patient privacy. Similarly, new diagnostics and risk prediction tools may result from basic science efforts, including those coming from neurodevelopmental trajectories [5, 6, 31] and epigenetic fingerprints, or patterns of DNA methylation or histone modifications that can be used to distinguish biological differences [32, 33]. Finally, recent research has supported the notion that researchers should consider adopting outcome measures that represent more proximal biological mechanisms, such as epigenetic mechanisms or microbiota, than more distal outcomes, given that these more proximal measures may be more sensitive to intervention efforts [11, 32, 34, 35].

Implementation of effective genomics-informed interventions depends on social and behavioral scientists being engaged in discovery. As well, optimal translation will require theory-driven intervention design that considers not only the behavioral and social factors important to intervention fidelity, but also the biological pathways that lead to positive health outcomes. Such interventions may not rely necessarily on the provision of genomic risk information, but may be tailored towards those who are particularly vulnerable based on their genetic susceptibility (e.g., at increased genetic risk for disease, sensitive to socio-environmental stressors, or a tendency to experience negative affective response to exercise) or may focus on the environmental exposures (e.g., toxins or social stress) that modulate gene expression.

PRIORITY 3: INCREASE OUTREACH AND EDUCATION EFFORTS TO IMPROVE THE PUBLIC’S GENOMIC LITERACY

Genomic literacy is a central component of optimal translation of genomic discoveries. This is true whether one considers provision of genetic risk information or engagement in genomics-informed behavioral interventions. Genomic literacy is defined as knowledge and understanding of genetic principles that allow one to make personal or clinical decisions on genetic issues [36]. It is comprised of several facets, including familiarity with genomic terms, skills needed to use genomic information, and factual knowledge of genomic principles that reflect a knowledge hierarchy such that each facet builds upon the one(s) prior [37]. A recent systematic review found that health care providers cite their own knowledge and skill deficits as being among the top barriers to integrating genomic medicine into the clinical encounter [38]. Relatedly, most respondents in a population-based sample demonstrated limited genomic-oriented skills and factual knowledge, which could be a serious detriment to making genomics-relevant personal decisions [37]. With large scale data projects such as All of Us providing more and more genomic information, now more than ever providers need to be equipped to use such knowledge effectively. Thus, there is significant need to develop educational and outreach programs to improve both providers’ and the general public’s genomic literacy levels.

There have been calls for the integration of genome or exome sequencing results into EHRs with the goal of improving clinical risk assessment. However, sequencing results are, by nature, complex, posing a challenge in communicating the meaning of such information to patients even while it resides in their EHR. Recognizing the importance of genomic literacy in optimal genomic medicine implementation, and in the context of societal decisions related to genomics (e.g., in legal or consumer settings), the Education and Community Involvement Branch at the National Human Genome Research Institute (NHGRI) recently established a new focus on genomic literacy education, the Genomic Literacy, Education and Engagement (GLEE) Initiative. At present, GLEE is envisioned to be a national initiative that will coordinate and augment ongoing genomics education and outreach efforts to enhance genomic literacy of healthcare providers and the general public.

To engage communities in dialogue related to genomic literacy, the Education and Community Involvement Branch has also established the Community Engagement in Genomics Working Group comprised of community liaisons and health advocates representing diverse populations to ensure that genomics and genomic medicine benefit all. The goals of the working group are to improve understanding of community’s varying perspectives and needs related to genomics, to engage and educate diverse communities about genomics, and to inform the NHGRI leadership of community priorities relevant to genomics research and related programs. Indeed, it is crucial to include key stakeholders and community members in planning stages for genomics research, particularly in intervention efforts that engage diverse populations.

PRIORITY 4: REPRESENTATION OF DIVERSE COMMUNITIES IN GENOMICS RESEARCH AND EQUITY OF ACCESS TO GENOMIC TECHNOLOGIES

Clinical integration of, and community-based behavioral interventions informed by, genomics benefit from consideration of the needs of underserved and vulnerable populations, including pediatric patients [39, 40], those who are cognitively impaired [41], those with limited access to care, and members of socially disadvantaged groups [42]. As well, throughout the entire basic research-to-translation pipeline, those involved in research, implementation, and policy need to be cognizant of the populations in which the initial research was conducted, and be aware that, for example, differences in genetic ancestry may impact risk and treatment. Clinicians will also need to consider equitable distribution of interventions and treatments; knowing that a patient is at genetic risk for a particular disease is of little use if the patient cannot afford the treatment or is geographically distant from the relevant clinic.

Genomics has the potential to refine how race and ethnicity are used in clinical practice, since self-identified race likely oversimplifies the roles of health, ancestry, and biological processes in disease [43]. However, in order for clinical translation to be relevant to all, there is a need to increase representation of ancestral heterogeneity in genomic discovery research. Most genomic discovery research is conducted on non-Hispanic white populations of higher socioeconomic status, yet there is an increasing amount of research showing a diversity in genetically-influenced differences in response to medications, disease risk, and associated risk factors. Not increasing the diversity of populations involved in translational efforts affects their health and increases health disparities [44, 45].

There are many concerns at the nexus of race, health disparities, and medical care which cannot be rehashed here. Suffice it to say that there is much left to be understood about the interplay among genomics, social and demographic factors (e.g., living conditions, economic status, access to healthful food and healthcare), and race with subsequent health outcomes. There may be very real differences in medical outcomes and conditions that vary in important ways based on the ancestral markers that are tied to self-identification of race. Genetic variants can affect risks for disease and how medications work, and these genetic variants can vary based on ancestry. A classic example is the APOE4 gene, which presents more frequently in populations with African ancestry, yet is more strongly associated with Alzheimer’s disease and its trajectory in populations of European ancestry [46]. Some important disease-relevant mutations were not even detected until diverse populations were included in genomic discovery. For example, research identified a mutation associated with substantially reduced breast cancer risk in Latinas with Indigenous American ancestry that does not seem to be present in individuals with other ancestries [47]. Research being conducted within the NIH IRP recently discovered, based on genome-wide analysis, African-specific variants significantly associated with obesity. Importantly, this risk variant has not been observed in populations of Asian or European ancestry, thus highlighting the importance of basic science research that engages diverse populations [48].

Individuals’ behavior affects their health, but these behaviors can also interact with and/or be influenced by one’s genetic makeup. The paucity of research investigating this interplay between genetic, and social and behavioral factors, as they relate to diverse populations points to the importance of increasing representation in discovery research. It is our view that expertise in community-based participatory approaches will be particularly important in engaging diverse communities in basic genetic discovery research, and will set the stage for optimal translation as it injects communities and their needs into the scientific conversation [49]. Reaching, recruiting, and engaging diverse communities in extramural initiatives such as All of Us is reliant on the expertise that social and behavioral scientists bring to the table. For such initiatives to generate results that truly have meaning for “all of us”, it is imperative that we take on leadership roles in such efforts. Taking on such leadership roles may require us to move outside of our comfort zone—to build transdisciplinary teams that include representation from biomedical sciences and to share our scientific discoveries at venues that will extend the reach of our message beyond the social and behavioral sciences.

CONCLUSION

The social and behavioral sciences clearly have a crucial role to play in next generation translational genomic research. This has been demonstrated clearly through basic social and behavioral sciences research aimed at understanding the interplay between biology and behavior, research on epigenetic mechanisms that may arise from gene–environment interactions, and investigation of key social pathways important to clinical and community translation of genomic information. This research often comes with challenges related to measurement, communication of complex concepts, and/or a need for increasingly collaborative science. In all, the goal is to reach everyone, including those typically underserved and those most vulnerable, by identifying important targets for implementation science that results in useful, transferable, and sustainable interventions or health education programs. Genomics offers an unprecedented opportunity for addressing these clinical and public health goals.

As social and behavioral scientists, it is exciting to see the natural integration of biomedical sciences, genetics and genomics, and social and behavioral sciences as new initiatives emerge from NIH. Approaches to understanding and promoting health and wellness have revolutionized to the point where there is little question about the need for such integration. With the influx of findings that will come from the initiatives and projects presented here, as well as other, equally innovative, projects will come the need for translation of these findings into useful tools that can be disseminated and implemented to broader communities. This need is being recognized by a burgeoning field of dissemination and implementation research, and we are excited about what is to come.

Compliance with ethical standards

Conflicts of interest: The authors have no conflicts of interest.

Ethical disclosures: This commentary is not an empirical paper and thus, did not require human subjects review.