Over the past century, genetics and genomics (“genomics”) have contributed significantly to our knowledge of human biology and disease. Genomics has also bolstered inaccurate and harmful arguments about “essential” differences between socially defined groups. These purported differences have reinforced class hierarchies and justified the mistreatment of groups such as Black people, Indigenous people, and other people of color and/or people with disabilities. With this history in mind, we explore how genomics is used to reinforce scientifically unsound understandings of the relationship between two fundamental aspects of the human experience: sex and gender. We argue that imprecise, inaccurate practices for collecting data and conducting genomic research have adversely influenced genomic science and can contribute to the stigmatization of people whose sex and/or gender challenge binary expectations. The results have been to preclude transgender and intersex people from accessing high-quality, evidence-based healthcare and to hinder their participation in scientifically sound research. In this perspective, we use the lens of queer theory to render this situation more visible. First, we highlight the theoretical contributions queer theory can make to genomic science. Second, we examine practices in research and clinical genomics that exclude and stigmatize transgender and intersex people. Third, we highlight the ways that many current genomic research practices generate false conclusions that are used to support unjust public policies. We conclude by recommending ways that clinicians and researchers can—and should—harness the scientific, social, and cultural power of genomics to advance knowledge and improve lives across the spectra of sex and gender.

Background: Limiting high-intensity exercise is recommended for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) due to its association with penetrance, arrhythmias, and structural progression. Guidelines recommend shared decision-making (SDM) for exercise level, but there is little evidence regarding its impact. Therefore, we sought to evaluate the extent and implications of SDM for exercise, decisional conflict, and decisional regret in patients with ARVC and at-risk relatives. Methods: Adults diagnosed with ARVC or with positive genetic testing enrolled in the Johns Hopkins ARVC Registry were invited to complete a questionnaire that included exercise history and current exercise, SDM (SDM-Q-9), decisional conflict, and decisional regret. Results: The response rate was 64.8%. Two-thirds of participants (68.0%, n=121) reported clinically significant decisional conflict regarding exercise at diagnosis/genetic testing (DCS [decisional conflict scale]≥25), and half (55.1%, n=98) in the past year. Prevalence of decisional regret was also high with 55.3% (n=99) reporting moderate to severe decisional regret (DRS [decisional regret scale]≥25). The extent of SDM was highly variable ranging from no (0) to perfect (100) SDM (mean, 59.6±25.0). Those diagnosed in adolescence (≤age 21) reported significantly more SDM ( P =0.013). Importantly, SDM was associated with less decisional conflict (ß=−0.66, R ² =0.567, P <0.01) and decisional regret (ß=−0.37, R ² =0.180, P <0.001) and no difference in vigorous intensity aerobic exercise in the 6 months after diagnosis/genetic testing or the past year ( P =0.56; P =0.34, respectively). Conclusions: SDM is associated with lower decisional conflict and decisional regret; and no difference in postdiagnosis exercise. Our data thus support SDM as the preferred model for exercise discussions for ARVC.

Background: Though genomic science has rapidly advanced, efforts to demonstrate the population-level utility of genomics have been slow to follow. It has long been argued that the family is an important unit of significance in genomics, yet it has been challenging to address this in clinical care. This is apparent in how hospital administrators and clinicians in the United States typically approach cascade screening, the process of notifying and offering genetic testing to at-risk relatives of a patient with a hereditary condition. The most common notification approach is proband-led contact, in which the index patient is responsible for communicating a health risk to their relatives. This model has been associated with suboptimal outcomes. In contrast, recent research has shown that system-led contact, in which healthcare or public health institutions initiate communication to relatives with the proband’s consent, has been associated with increased clinical utility and acceptability. Summary: With the needs of hospital administrators and clinicians in mind, we revisit normative questions about the appropriate way to notify relatives about their potentially elevated risk of developing an actionable disease. We review evidence demonstrating that system-led direct contact of relatives is feasible and acceptable. We further argue that system-led contact of relatives eligible for cascade screening is ethically justified if these programs are designed with public input, have an opt-out provision, and are implemented for conditions that meet specific criteria which we propose in this article. Key Messages: In this article, we emphasize the usefulness of public health ethics frameworks to inform the design of system-led contact programs. Beyond this, we make the case that such programs are necessary to realize the population utility of genomic medicine equitably.