Julia M. Crouch

Attitudes of African Americans Toward Return of Results From Exome and Whole Genome Sequencing

Exome sequencing and whole genome sequencing (ES/WGS) present patients and research participants with the opportunity to benefit from a broad scope of genetic results of clinical and personal utility. Yet, this potential for benefit also risks disenfranchising populations such as African Americans (AAs) that are already underrepresented in genetic research and utilize genetic tests at lower rates than other populations. Understanding a diverse range of perspectives on consenting for ES/WGS and receiving ES/WGS results is necessary to ensure parity in genomic health care and research. We conducted a series of 13 focus groups (n = 76) to investigate if and how attitudes toward participation in ES/WGS research and return of results from ES/WGS differ between self‐described AAs and non‐AAs. The majority of both AAs and non‐AAs were willing to participate in WGS studies and receive individual genetic results, but the fraction not interested in either was higher in AAs. This is due in part to different expectations of health benefits from ES/WGS and how results should be managed. Our results underscore the need to develop and test culturally tailored strategies for returning ES/WGS results to AAs.

Attitudes of non-African American focus group participants toward return of results from exome and whole genome sequencing.

Exome sequencing and whole genome sequencing (ES/WGS) present individuals with the opportunity to benefit from a broad scope of genetic results of clinical and personal utility. Yet, it is unclear which genetic results people want to receive (i.e., what type of genetic information they want to learn about themselves) or conversely not receive, and how they want to receive or manage results over time. Very little is known about whether and how attitudes toward receiving individual results from ES/WGS vary among racial/ethnic populations. We conducted 13 focus groups with a racially and ethnically diverse parent population (n = 76) to investigate attitudes toward return of individual results from WGS. We report on our findings for non‐African American (non‐AA) participants. Non‐AA participants were primarily interested in genetic results on which they could act or “do something about.” They defined “actionability” broadly to include individual medical treatment and disease prevention. The ability to plan for the future was both a motivation for and an expected benefit of receiving results. Their concerns focused on the meaning of results, specifically the potential inaccuracy and uncertainty of results. Non‐AA participants expected healthcare providers to be involved in results management by helping them interpret results in the context of their own health and by providing counseling support. We compare and contrast these themes with those we previously reported from our analysis of African American (AA) perspectives to highlight the importance of varying preferences for results, characterize the central role of temporal orientation in framing expectations about the possibility of receiving ES/WGS results, and identify potential avenues by which genomic healthcare disparities may be inadvertently perpetuated.

Population description and its role in the interpretation of genetic association

Despite calls for greater clarity and precision of population description, studies have documented persistent ambiguity in the use of race/ethnicity terms in genetic research. It is unclear why investigators tolerate such ambiguity, or what effect these practices have on the evaluation of reported associations. To explore the way that population description is used to replicate and/or extend previously reported genetic observations, we examined articles describing the association of the peroxisome proliferator-activated receptor-gamma-γ Pro12Ala polymorphism with type 2 diabetes mellitus and related phenotypes, published between 1997 and 2005. The 80 articles identified were subjected to a detailed content analysis to determine (1) how sampled populations were described, (2) whether and how the choice of sample was explained, and (3) how the allele frequency and genetic association findings identified were contextualized and interpreted. In common with previous reports, we observed a variety of sample descriptions and little explanation for the choice of population investigated. Samples of European origin were typically described with greater specificity than samples of other origin. However, findings from European samples were nearly always compared to samples described as “Caucasian” and sometimes generalized to all Caucasians or to all humans. These findings suggest that care with population description, while important, may not fully address analytical concerns regarding the interpretation of variable study outcomes or ethical concerns regarding the attribution of genetic observations to broad social groups. Instead, criteria which help investigators better distinguish justified and unjustified forms of population generalization may be required.

My46: a Web-based tool for self-guided management of genomic test results in research and clinical settings.

A major challenge to implementing precision medicine is the need for an efficient and cost-effective strategy for returning individual genomic test results that is easily scalable and can be incorporated into multiple models of clinical practice. My46 is a Web-based tool for managing the return of genetic results that was designed and developed to support a wide range of approaches to disclosing results, ranging from traditional face-to-face disclosure to self-guided models. My46 has five key functions: set and modify results-return preferences, return results, educate, manage the return of results, and assess the return of results. These key functions are supported by six distinct modules and a suite of features that enhance the user experience, ease site navigation, facilitate knowledge sharing, and enable results-return tracking. My46 is a potentially effective solution for returning results and supports current trends toward shared decision making between patients and providers and patient-driven health management.Genet Med 19 4, 467–475.

“We Don’t Know Her History, Her Background”: Adoptive Parents’ Perspectives on Whole Genome Sequencing Results

Exome sequencing and whole genome sequencing (ES/WGS) can provide parents with a wide range of genetic information about their children, and adoptive parents may have unique issues to consider regarding possible access to this information. The few papers published on adoption and genetics have focused on targeted genetic testing of children in the pre-adoption context. There are no data on adoptive parents’ perspectives about pediatric ES/WGS, including their preferences about different kinds of results, and the potential benefits and risks of receiving results. To explore these issues, we conducted four exploratory focus groups with adoptive parents (N = 26). The majority lacked information about their children’s biological family health history and ancestry, and many viewed WGS results as a way to fill in these gaps in knowledge. Some expressed concerns about protecting their children’s future privacy and autonomy, but at the same time stated that WGS results could possibly help them be proactive about their children’s health. A few parents expressed concerns about the risks of WGS in a pre-adoption context, specifically about decreasing a child’s chance of adoption. These results suggest that issues surrounding genetic information in the post-adoption and ES/WGS contexts need to be considered, as well as concerns about risks in the pre-adoption context. A critical challenge for ES/WGS in the context of adoption will be balancing the right to know different kinds of genetic information with the right not to know. Specific guidance for geneticists and genetic counselors may be needed to maximize benefits of WGS while minimizing harms and prohibiting misuse of the information in the adoption process.

Personalized medicine and tobacco-related health disparities: is there a role for genetics?

Genetic testing has been proposed as a means to increase smoking cessation rates and thus reduce smoking prevalence. To understand how that might be practically possible, with appreciation of the current social context of tobacco use and dependence, we performed a contextual analysis of smoking-related genetics and smoking cessation. To provide added value, genetics would need to inform and improve existing interventions for smokers (including behavioral and pharmacological treatments). Pharmacogenetics offers the most promising potential, because it may improve the efficacy of medication-based smoking cessations strategies. All proven interventions for treating tobacco dependence, however, including simple cost-effective measures, such as quit lines and physician counseling, are underutilized. As tobacco use occurs disproportionately among disadvantaged populations, efforts to improve smokers’ access to health care, and to the tools that are known to help them quit, represent the most promising approaches for reducing smoking prevalence within these groups. Similar considerations apply to other chronic diseases contributing to population-level health disparities. We conclude that although genetics offers increasing opportunities to tailor drug treatment, and may in some cases provide useful risk prediction, other methods of personalizing care are likely to yield greater benefit to populations experiencing health disparities related to tobacco use.

Youth and caregiver experiences of gender identity transition: A qualitative study.

Gender identity formation is a key part of normal adolescent development (Stieglitz, 2010). For transgender youth this is a multistage process that can be challenging both for the youth and for their families. In this sub analysis, we describe the journey transgender youth and their families experience throughout the stages of transitioning. Perspectives were solicited from transgender youth (age 14–22 years) and parents of transgender youth. Theoretical thematic analysis was used to find common themes using Atlas.ti software. Thirty-three participants (15 youth, 18 parents) were recruited, 16 of which were interviewed. Analysis revealed almost all of the youth and caregiver participants initially lacked the language and knowledge to accurately describe feelings of gender confusion. Once embarking on the transition process participants experienced both positive and negative reactions from families, friends and peers, school administrators and providers. However, all participants described transitioning as a rewarding and vital experience. Finally, many participants reported needing and or seeking mental health care, but experienced barriers. Youth and caregivers described varying experiences for youth throughout the recognition, coming out and transitioning process that impacted the journey. This is one of the first studies to collect an in-depth recall of the transitioning process from youth and caregiver perspectives, giving youth and families a voice to enable a greater understanding of the process of gender transition during adolescence.

Use of metaphors about exome and whole genome sequencing.

Clinical and research uses of exome and whole genome sequencing (ES/WGS) are growing rapidly. An enhanced understanding of how individuals conceptualize and communicate about sequencing results is needed to ensure effective, mutual exchange of information between care providers and patients and between researchers and participants. Focus groups and interviews participants were recruited to discuss their attitudes and preferences for receiving hypothetical results from ES/WGS. African Americans were intentionally oversampled. We qualitatively analyzed participants’ speech to identify unsolicited metaphorical language pertaining to genes and health, and grouped these occurrences into metaphorical concepts. Participants compared genetic information to physical objects including tools, weapons, contents of boxes, and formal documents or reports. These metaphorical concepts centered on several key themes, including locus of control; containment versus release of information; and desirability, usability, interpretability, and ownership of genetic results. Metaphorical language is often used intentionally or unintentionally in discussions about receiving results from ES/WGS in both clinical and research settings. Awareness of the use of metaphorical language and attention to its varied meanings facilitates effective communication about return of ES/WGS results. In turn, both should foster shared and informed decision‐making and improve the translation of genetic information by clinicians and researchers.