Annual Review of Genomics and Human Genetics - Volume 14, 2013

An enduring goal of evolutionary biology is to understand how natural selection has shaped patterns of polymorphism and divergence within and between species and to map the genetic basis of adaptations. The rapid maturation of next-generation sequencing technology has generated a deluge of genomics data from nonhuman primates, extinct hominins, and diverse human populations. These emerging genome data sets have simultaneously broadened our understanding of human evolution and sharply defined existing gaps in knowledge about the mechanistic basis of evolutionary change. In this review, we summarize recent insights into how natural selection has influenced the human genome across different timescales. Although the path to a more comprehensive understanding of selection and adaptation in humans remains arduous, some general insights are beginning to emerge, such as the importance of adaptive regulatory evolution, the absence of pervasive classic selective sweeps, and the potential roles that selection from standing variation and polygenic adaptation have likely played in recent human evolutionary history.

Communicating genetic risk information in ways that maximize understanding and promote health is increasingly important given the rapidly expanding availability and capabilities of genomic technologies. A well-developed literature on risk communication in general provides guidance for best practices, including presentation of information in multiple formats, attention to framing effects, use of graphics, sensitivity to the way numbers are presented, parsimony of information, attentiveness to emotions, and interactivity as part of the communication process. Challenges to communicating genetic risk information include deciding how best to tailor it, streamlining the process, deciding what information to disclose, accepting that communications may have limited influence, and understanding the impact of context. Meeting these challenges has great potential for empowering individuals to adopt healthier lifestyles and improve public health, but will require multidisciplinary approaches and collaboration.

The field of behavioral genetics has engendered a host of moral and social concerns virtually since its inception. The policy implications of a genetic basis for behaviors are widespread and extend beyond the clinic to the socially important realms of education, criminal justice, childbearing, and child rearing. The development of new techniques and analytic approaches, including whole-genome sequencing, noninvasive prenatal genetic testing, and optogenetics, has clearly changed the study of behavioral genetics. However, the social context of biomedical research has also changed profoundly over the past few decades, and in ways that are especially relevant to behavioral genetics. The ever-widening scope of behavioral genetics raises ethical, legal, social, and policy issues in the potential new applications to criminal justice, education, the military, and reproduction. These issues are especially critical to address because of their potentially disproportionate effects on vulnerable populations such as children, the unborn, and the incarcerated.

Whole-genome sequencing (WGS) has advanced to a point where it is beginning to be integrated into pediatric practice. With little consensus on how to maximize the benefits of WGS for children, there is a growing need for focused efforts that connect researchers, clinicians, and families to chart a path forward. To illustrate relevant concerns, two contrasting applications of pediatric WGS are explored: clinical use with children who have undiagnosed conditions, and population-based screening. Specific challenges for health care services, policy development, and the well-being of children are discussed in light of current research. In the interest of ensuring evidence-based pediatric WGS, strategies are identified for advancing our understanding of what it means for children to grow up with WGS results guiding their health care.

The debate over return of individual research results and incidental findings to study participants is a key frontier in research ethics and practice. This is fundamentally a problem of translational science—a question of when information about an individual that is generated in research should be communicated for clinical attention, particularly as technologies such as whole-genome sequencing and whole-exome sequencing are increasingly used in clinical care. There is growing consensus that investigators should offer participants at least those individual findings of high clinical importance and actionability. Increasing attention to what information biobanks and secondary researchers owe people who provide data and specimens offers an opportunity to treat these source individuals as research partners. Cutting-edge issues include return of results in pediatric populations and return to kin and family, both before and after the death of the proband, as well as how to manage incidental findings in clinical sequencing. Progress will require an understanding of the continuum linking research and clinical care and developing standards and models for return.

Patient advocacy organizations (PAOs) are nonprofit groups that represent patients and families affected by a significant medical condition or disease. We review some of the different approaches that humanities and social researchers use to study PAOs. Drawing on this recent scholarship, we describe some contemporary patient groups and explore how PAOs can collaborate with biomedical researchers to advance genomic science. We highlight research that aims to describe how PAOs are contributing to multiple aspects of biomedical research, including study design, definition of research goals, data collection and analysis, dissemination of results, and research funding. We also describe several challenges that genomic researchers may encounter in collaborations with PAOs. Throughout our review, we focus on the manner in which new PAO roles challenge traditional boundaries between researchers and subjects, thereby redefining the relationship of patients to science. We consider how this shift may affect our view of scientific collaborations and impact genomic researchers in the future.