Is there a way to reduce the inequity in variant interpretation on the basis of ancestry?

The underrepresentation of non-European ancestry groups in current genomic databases complicates interpretation of their genetic test results, yielding a much higher prevalence of variants of uncertain significance (VUSs). Such VUS findings can frustrate the goals of genetic testing, create anxiety in patients, and lead to unnecessary medical interventions. Approaches to addressing underrepresentation of people with genetic ancestries other than European are being undertaken by broad-based recruitment efforts.

Three legs of the missing heritability problem.

The so-called 'missing heritability problem' is often characterized by behavior geneticists as a numerical discrepancy between alternative kinds of heritability. For example, while 'traditional heritability' derived from twin and family studies indicates that approximately ∼50% of variation in intelligence is attributable to genetics, 'SNP heritability' derived from genome-wide association studies indicates that only ∼10% of variation in intelligence is attributable to genetics. This 40% gap in variance accounted for by alternative kinds of heritability is frequently referred to as what's "missing.

The Challenge of Genetic Variants of Uncertain Clinical Significance : A Narrative Review.

Genomic tests expand diagnostic and screening opportunities but also identify genetic variants of uncertain clinical significance (VUSs). Only a minority of VUSs are likely to prove pathogenic when later reassessed, but resolution of the uncertainty is rarely timely. That uncertainty adds complexity to clinical decision making and can result in harms and costs to patients and the health care system, including the time-consuming analysis required to interpret a VUS and the potential for unnecessary treatment and adverse psychological effects.

Polygenic embryo testing: understated ethics, unclear utility.

New technologies are expanding the reach and accessibility of pre-implantation genetic testing of human embryos. But what these advances can deliver is still unclear and a frank assessment of their profound ethical implications is crucial.

Patient and Caregiver Experiences With and Perceptions of Risk Evaluation and Mitigation Strategy Programs With Elements to Assure Safe Use.

Importance: The US Food and Drug Administration (FDA) Amendments Act of 2007 authorized the FDA to impose safety requirements on drugs with important risks, such as prescriber certification or routine laboratory testing, to ensure that the benefits of use outweighed the risks. However, little is known about patient and caregiver experiences with these Risk Evaluation and Mitigation Strategy (REMS) programs with Elements to Assure Safe Use (ETASU).

Objective: To understand patient and caregiver experiences with and perceptions of REMS programs with ETASU.

Patients' roles in governance of learning: Results from a qualitative study of 16 learning healthcare systems.

Patient and family engagement has been identified as key to fulfilling Learning Healthcare Systems' (LHSs') promise as a model for improving clinical care, catalyzing research, and controlling costs. Little is known, however, about the state of patient engagement in the learning mission of these systems or about what governance structures and processes facilitate such engagement. Here, we report on an interview study of 99 patient and employee leaders in 16 systems.

Bioethics and Gerontology: The Value of Thinking Together.

The interdisciplinary field of bioethics focuses on what it means to be a person, flourish as a person, and be respected as a person in different conditions of health, illness, or disability. Bioethics and policy research considers normative questions such as how a good society, through its priorities and investments, should demonstrate its commitments to the lives of different populations. Bioethics and humanities scholarship, often known as "health humanities," shares affinities with age studies and disability studies and with narrative-based approaches to the study of human experience.

Half a century later and we're back where we started: How the problem of locality turned in to the problem of portability.

In the 1970s, Lewontin sparked a debate about a problem of locality, by making the case that any given heritability estimate is local to the original population and environment studied, and could not be generalized to other populations and environments. Nearly 50 years later, a new problem of portability has emerged: the predictive accuracy of polygenic scores diminishes when applied to populations whose characteristics are different from the original population sample. This paper briefly reviews the nature of each problem and analyzes their similarities and differences in three areas: 1) conceptual underpinnings, 2) causal explanations, and 3) practical, social, and political implications.

FoGS provides a public FAQ repository for social and behavioral genomic discoveries.

Here we introduce ‘FAQs on Genomic Studies’ (FoGS), an open-access repository of explanatory documents that accompany genomic analyses in social and behavioral genomics. For fields such as social and behavioral genomics that are shaped by an ugly history and uncertain future, socially and ethically responsible research and research communication are crucial. FoGS amplifies one such approach towards responsible research communication.

Recommendations for Responsible Development and Application of Neurotechnologies.

Advancements in novel neurotechnologies, such as brain computer interfaces (BCI) and neuromodulatory devices such as deep brain stimulators (DBS), will have profound implications for society and human rights. While these technologies are improving the diagnosis and treatment of mental and neurological diseases, they can also alter individual agency and estrange those using neurotechnologies from their sense of self, challenging basic notions of what it means to be human. As an international coalition of interdisciplinary scholars and practitioners, we examine these challenges and make recommendations to mitigate negative consequences that could arise from the unregulated development or application of novel neurotechnologies.

The need for a unified ethical stance on child genital cutting.

The American College of Nurse-Midwives, American Society for Pain Management Nursing, American Academy of Pediatrics, and other largely US-based medical organizations have argued that at least some forms of non-therapeutic child genital cutting, including routine penile circumcision, are ethically permissible even when performed on non-consenting minors. In support of this view, these organizations have at times appealed to potential health benefits that may follow from removing sexually sensitive, non-diseased tissue from the genitals of such minors. We argue that these appeals to "health benefits" as a way of justifying medically unnecessary child genital cutting practices may have unintended consequences.

Male or female genital cutting: why 'health benefits' are morally irrelevant.

The WHO, American Academy of Pediatrics and other Western medical bodies currently maintain that all medically unnecessary female genital cutting of minors is categorically a human rights violation, while either tolerating or actively endorsing medically unnecessary male genital cutting of minors, especially in the form of penile circumcision. Given that some forms of female genital cutting, such as ritual pricking or nicking of the clitoral hood, are less severe than penile circumcision, yet are often performed within the same families for similar (eg, religious) reasons, it may seem that there is an unjust double standard. Against this view, it is sometimes claimed that while female genital cutting has 'no health benefits', male genital cutting has at least some.

Inequalities in avoidable hospitalisation in large urban areas: retrospective observational study in the metropolitan area of Milan.

Objective: Significant inequalities in access to healthcare system exist between residents of world megacities, even if they have different healthcare systems. The aim of this study was to estimate avoidable hospitalisations in the metropolitan area of Milan (Italy) and explore inequalities in access to healthcare between patients and across their areas of residence.

Design: Retrospective observational study.

Hospice Access and Scope of Services for Undocumented Immigrants: A Clinician Survey.

To characterize clinician experiences of hospice access and scope of services for undocumented immigrants. The 10.5 million undocumented immigrants in the United States are not covered by Medicare's hospice benefit and are at high risk for being uninsured.