Development of a digital risk-prediction tool based on family health history for the general population: legal and ethical implications.

Cardiovascular diseases, both inherited and familial, indicate a risk of early and preventable cardiovascular events for relatives of affected individuals. A digital risk-prediction tool that enables general population individuals to evaluate their cardiovascular risk based on family health history could be a responsible approach to facilitate early detection and improve public health, but development and use of such a tool is not without legal and ethical requirements. At the start of tool development, experts addressed potential legal and ethical implications.

Ethical considerations in prenatal genomic testing.

This paper discusses ethical issues arising in the context of prenatal genomic testing. While genomic information in the prenatal context might increase reproductive choice, e.g.

Why digital innovation may not reduce healthcare's environmental footprint.

In order for digital innovations to have a positive role in efforts to make healthcare more environmentally sustainable, it is important to understand the environmental consequences of investment in digital infrastructure, argue Samuel and colleagues.

Genomics and insurance in the United Kingdom: increasing complexity and emerging challenges.

This article identifies issues relating to the use of genetics and genomics in risk-rated insurance that may challenge existing regulatory models in the UK and elsewhere. We discuss three core issues: (1) As genomic testing advances, and results are increasingly relevant to guide healthcare across an individual's lifetime, the distinction between diagnostic and predictive testing that the current UK insurance code relies on becomes increasingly blurred. (2) The emerging category of pharmacogenetic tests that are predictive only in the context of a specific prescribing moment.

Predictive genetic testing for Huntington's disease: Exploring participant experiences of uncertainty and ambivalence between clinic appointments.

Ambivalence and uncertainty are key themes throughout the psychology of healthcare literature. This is especially so for individuals at risk of Huntington's disease (HD) deliberating the decision to undergo genetic testing because there is currently no treatment that modifies disease progression. A better understanding of the experience of making a decision about genetic prediction will help practitioners support and guide individuals through this process.

The ethical challenges of diversifying genomic data: A qualitative evidence synthesis.

This article aims to explore the ethical issues arising from attempts to diversify genomic data and include individuals from underserved groups in studies exploring the relationship between genomics and health. We employed a qualitative synthesis design, combining data from three sources: 1) a rapid review of empirical articles published between 2000 and 2022 with a primary or secondary focus on diversifying genomic data, or the inclusion of underserved groups and ethical issues arising from this, 2) an expert workshop and 3) a narrative review. Using these three sources we found that ethical issues are interconnected across structural factors and research practices.

Systematic reanalysis of genomic data by diagnostic laboratories: a scoping review of ethical, economic, legal and (psycho)social implications.

With the introduction of Next Generation Sequencing (NGS) techniques increasing numbers of disease-associated variants are being identified. This ongoing progress might lead to diagnoses in formerly undiagnosed patients and novel insights in already solved cases. Therefore, many studies suggest introducing systematic reanalysis of NGS data in routine diagnostics.

Ethical preparedness in genomic medicine: how NHS clinical scientists navigate ethical issues.

Much has been published about the ethical issues encountered by clinicians in genetics/genomics, but those experienced by clinical laboratory scientists are less well described. Clinical laboratory scientists now frequently face navigating ethical problems in their work, but how they should be best supported to do this is underexplored. This lack of attention is also reflected in the ethics tools available to clinical laboratory scientists such as guidance and deliberative ethics forums, developed primarily to manage issues arising within the clinic.

"A very big challenge": a qualitative study to explore the early barriers and enablers to implementing a national genomic medicine service in England.

The Genomic Medicine Service (GMS) was launched in 2018 in England to create a step-change in the use of genomics in the NHS, including offering whole genome sequencing (WGS) as part of routine care. In this qualitative study on pediatric rare disease diagnosis, we used an implementation science framework to identify enablers and barriers which have influenced rollout. Semi-structured interviews were conducted with seven participants tasked with designing the GMS and 14 tasked with leading the implementation across the seven Genomic Medicine Service Alliances (GMSAs) and/or Genomic Laboratory Hubs (GLHs) between October 2021 and February 2022.

Prospective study design and data analysis in UK Biobank.

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.

Secondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure.

Purpose: The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, and costs.

Methods: An observational study in an area representing one-fifth of England.

Glowing gels and pipettes aplenty: how do commercial stock image banks portray genetic tests?

News stories and patient-facing material about genetic tests are often illustrated by images, but the content of such images and the messages they propagate are rarely scrutinised. Stock image banks were searched to identify a hundred images relating to genetic tests and analysed using a multimodal critical discourse approach, aiming to identify what the images featured, how they were composed, and what they communicated about genetic testing. We found that images tended to focus on technical aspects of sample processing (for example, pipetting) and drew on older technologies (for example slab gel electrophoresis) when representing data arising from genetic tests.

Ancestry, race and ethnicity: the role and relevance of language in clinical genetics practice.

Background: The terms ancestry, race and ethnicity are used variably within the medical literature and within society and clinical care. Biological lineage can provide an important context for the interpretation of genomic data, but the language used, and practices around when to ascertain this, vary.

Methods: Using a fictional case scenario we explore the relevance of questions around ancestry, race and ethnicity in clinical genetic practice.

Retrospective Cohort Study on the Limitations of Direct-to-Consumer Genetic Screening in Hereditary Breast and Ovarian Cancer.

Purpose: Among cancer predisposition genes, most direct-to-consumer (DTC) genetic tests evaluate three Ashkenazi Jewish (AJ) founder mutations in , which represent a small proportion of pathogenic or likely pathogenic variants (PLPV) in cancer predisposing genes. In this study, we investigate PLPV in and other cancer predisposition genes that are missed by testing only AJ founder mutations.

Methods: Individuals were referred to genetic testing for personal diagnoses of breast and/or ovarian cancer (clinical cohort) or were self-referred (nonindication-based cohort).

Interventions to support patients with sharing genetic test results with at-risk relatives: a synthesis without meta-analysis (SWiM).

Whilst the finding of heritable susceptibility to disease was once relatively rare, mainstreaming of genetic testing has resulted in a steady increase. Patients are often encouraged to share their genetic test results with relevant relatives, but relatives may not receive this information, leaving them without knowledge of their own risk. Therefore, strategies to help communicate such information are important.

Discussion of off-target and tentative genomic findings may sometimes be necessary to allow evaluation of their clinical significance.

We discuss a case where clinical genomic investigation of muscle weakness unexpectedly found a genetic variant that might (or might not) predispose to kidney cancer. We argue that despite its off-target and uncertain nature, this variant should be discussed with the man who had the test, not because it is medical information, but because this discussion would allow the further clinical evaluation that might lead it to becoming so. We argue that while prominent ethical debates around genomics often take 'results' as a starting point and ask questions as to whether to look for and how to react to them, the construction of genomic results is fraught with ethical complexity, although often couched as a primarily technical problem.

Ethical preparedness and developments in genomic healthcare.

Considerations of the notion of preparedness have come to the fore in the recent pandemic, highlighting a need to be better prepared to deal with sudden, unexpected and unwanted events. However, the concept of preparedness is also important in relation to planned for and desired interventions resulting from healthcare innovations. We describe ethical preparedness as a necessary component for the successful delivery of novel healthcare innovations, and use recent advances in genomic healthcare as an example.