Potential corporate uses of polygenic indexes: Starting a conversation about the associated ethics and policy issues.

Some commercial firms currently sell polygenic indexes (PGIs) to individual consumers, despite their relatively low predictive power. It might be tempting to assume that because the predictive power of many PGIs is so modest, other sorts of firms-such as those selling insurance and financial services-will not be interested in using PGIs for their own purposes. We argue to the contrary. We build this argument in two ways. First, we offer a very simple model, rooted in economic theory, of a profit-maximizing firm that can gain information about a single consumer's genome. We use the model to show that, depending on the specific economic environment, a firm would be willing to pay for statistically noisy PGIs, even if they allow for only a small reduction in uncertainty. Second, we describe two plausible scenarios in which these different kinds of firms could conceivably use PGIs to maximize profits. Finally, we briefly discuss some of the associated ethics and policy issues. They deserve more attention, which is unlikely to be given until it is first recognized that firms whose services affect a large swath of the public will indeed have incentives to use PGIs.

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. Introduction will, however, also have ethical, economic, legal and (psycho)social (ELSI) implications that Genetic Health Professionals (GHPs) from laboratories should consider before possible implementation of systematic reanalysis. To get a first impression we performed a scoping literature review. Our findings show that for the vast majority of included articles ELSI aspects were not mentioned as such. However, often these issues were raised implicitly. In total, we identified nine ELSI aspects, such as (perceived) professional responsibilities, implications for consent and cost-effectiveness. The identified ELSI aspects brought forward necessary trade-offs for GHPs to consciously take into account when considering responsible implementation of systematic reanalysis of NGS data in routine diagnostics, balancing the various strains on their laboratories and personnel while creating optimal results for new and former patients. Some important aspects are not well explored yet. For example, our study shows GHPs see the values of systematic reanalysis but also experience barriers, often mentioned as being practical or financial only, but in fact also being ethical or psychosocial. Engagement of these GHPs in further research on ELSI aspects is important for sustainable implementation.

Ready for polygenic risk scores? An analysis of regulation of preimplantation genetic testing in European countries.

STUDY QUESTION: Would the different regulatory approaches for preimplantation genetic testing (PGT) in Europe permit the implementation of preimplantation genetic testing using polygenic risk scores (PGT-P)? SUMMARY ANSWER: While the regulatory approaches for PGT differ between countries, the space provided for potential implementation of PGT-P seems limited in all three regulatory models. WHAT IS KNOWN ALREADY: PGT is a reproductive genetic technology that allows the testing for hereditary genetic disorders and chromosome abnormalities in embryos before implantation. Throughout its history, PGT has largely been regarded as an ethically sensitive technology. For example, ethical questions have been raised regarding the use of PGT for adult-onset conditions, non-medical sex selection, and human leukocyte antigen typing for the benefit of existing siblings. Countries in which PGT is offered each have their own approach of regulating the clinical application of PGT, and a clear overview of legal and practical regulation of PGT in Europe is lacking. An emerging development within the field of PGT, namely PGT-P, is currently bringing new ethical tensions to the forefront. It is unclear whether PGT-P may be applied within the current regulatory frameworks in Europe. Therefore, it is important to investigate current regulatory frameworks in Europe and determine whether PGT-P fits within these frameworks. STUDY DESIGN, SIZE, DURATION: The aim of this study was to provide an overview of the legal and practical regulation of the use of PGT in seven selected European countries (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK) and critically analyse the different approaches with regards to regulatory possibilities for PGT-P. Between July and September 2023, we performed a thorough and extensive search of websites of governments and governmental agencies, websites of scientific and professional organizations, and academic articles in which laws and regulations are described. PARTICIPANTS/MATERIALS, SETTING, METHODS: We investigated the legal and regulatory aspects of PGT by analysing legal documents, regulatory frameworks, scientific articles, and guidelines from scientific organizations and regulatory bodies to gather relevant information about each included country. The main sources of information were national laws relating to PGT. MAIN RESULTS AND THE ROLE OF CHANCE: We divided the PGT regulation approaches into three models. The regulation of PGT differs per country, with some countries requiring central approval of PGT for each new indication (the medical indication model: the UK, the Netherlands), other countries evaluating each individual PGT request at the local level (the individual requests model: France, Germany), and countries largely leaving decision-making about clinical application of PGT to healthcare professionals (the clinical assessment model: Belgium, Italy, Spain). In the countries surveyed that use the medical indication model and the individual requests model, current legal frameworks and PGT criteria seem to exclude PGT-P. In countries using the clinical assessment model, the fact that healthcare professionals and scientific organizations in Europe are generally negative about implementation of PGT-P due to scientific and socio-ethical concerns, implies that, even if it were legally possible, the chance that PGT-P would be offered in the near future might be low. LIMITATIONS, REASONS FOR CAUTION: The results are based on our interpretation of publicly available written information and documents, therefore not all potential discrepancies between law and practice might have been identified. In addition, our analysis focuses on seven-and not all-European countries. However, since these countries are relevant players within PGT in Europe and since they have distinct PGT regulations, the insights gathered give relevant insights into diverse ways of PGT regulation. WIDER IMPLICATIONS OF THE FINDINGS: To the best of our knowledge, this is the first paper that provides a thorough overview of the legal and practical regulation of PGT in Europe. Our analysis of how PGT-P fits within current regulation models provides guidance for healthcare professionals and policymakers in navigating the possible future implementation of PGT-P within Europe. STUDY FUNDING/COMPETING INTEREST(S): This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 813707. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Is It Just for a Screening Program to Give People All the Information They Want?

Genomic screening at population scale generates many ethical considerations. One is the normative role that people's preferences should play in determining access to genomic information in screening contexts, particularly information that falls beyond the scope of screening. We expect both that people will express a preference to receive such results and that there will be interest from the professional community in providing them. In this paper, we consider this issue in relation to the just and equitable design of population screening programs like reproductive genetic carrier screening (RGCS). Drawing on a pluralistic public health ethics perspective, we claim that generating and reporting information about genetic variants beyond the scope of the screening program usually lacks clinical, and perhaps personal, utility. There are both pragmatic and ethical reasons to restrict information provision to that which fits the stated purpose of the program.

Public views on polygenic screening of embryos.

Understanding moral acceptability and willingness to use is crucial for informing policy.

Sequencing projects will screen 200,000 newborns for disease.

U.K. and New York City efforts face cost and ethical issues.

Genetic data sharing and artificial intelligence in the era of personalized medicine based on a cross-sectional analysis of the Saudi human genome program.

The success of the Saudi Human Genome Program (SHGP), one of the top ten genomic programs worldwide, is highly dependent on the Saudi population embracing the concept of participating in genetic testing. However, genetic data sharing and artificial intelligence (AI) in genomics are critical public issues in medical care and scientific research. The present study was aimed to examine the awareness, knowledge, and attitude of the Saudi society towards the SHGP, the sharing and privacy of genetic data resulting from the SHGP, and the role of AI in genetic data analysis and regulations. Results of a questionnaire survey with 804 respondents revealed moderate awareness and attitude towards the SHGP and minimal knowledge regarding its benefits and applications. Respondents demonstrated a low level of knowledge regarding the privacy of genetic data. A generally positive attitude was found towards the outcomes of the SHGP and genetic data sharing for medical and scientific research. The highest level of knowledge was detected regarding AI use in genetic data analysis and privacy regulation. We recommend that the SHGP's regulators launch awareness campaigns and educational programs to increase and improve public awareness and knowledge regarding the SHGP's benefits and applications. Furthermore, we propose a strategy for genetic data sharing which will facilitate genetic data sharing between institutions and advance Personalized Medicine in genetic diseases' diagnosis and treatment.

Physicians' perceptions of the factors influencing disclosure of secondary findings in tumour genomic profiling in Japan: a qualitative study.

Tumour genomic profiling (TGP), conducted in search of therapeutics, sometimes reveals potentially pathogenic germline variants as secondary findings (SFs). Physicians involved in TGP are often specialised in oncology and not in clinical genetics. To better utilise SFs, we explored issues physicians have during disclosure and the potential for collaborations with clinical genetics professionals. Semi-structured interviews were conducted with 14 physicians who had experience in handling outpatient TGP at designated core hospitals for cancer genomic medicine in Japan. The data were analysed thematically. The difficulties physicians experienced during informed consent (IC) included educating patients about SFs, providing detailed information on SFs, and explaining the impact of SFs on patients' family members. When SFs were detected, physicians had reservations regarding the relevance of the disclosure criteria. Confirmatory germline tests were performed using peripheral blood when tumour-only tests detected suspected SFs. Some physicians had reservations about the necessity of confirmatory tests when they did not affect the patients' treatment options. To encourage patients to receive confirmatory tests, improvements are necessary in the healthcare system, such as insurance reimbursements, education for physicians so that they can provide a better explanation to their patients, and genetic literacy of physicians and patients. The physicians offered insights into the challenges they experienced related to IC, disclosure of SFs, and expectations for active collaborations with clinical genetics professionals. Wider healthcare insurance coverage and better genetic literacy of the population may lead to more patients taking confirmatory tests when SFs are suspected.

Uptake and Patient Perspectives on Additional Testing for Novel Disease-Associated Genes: Lessons from a PAH Cohort.

BACKGROUND: Pulmonary arterial hypertension (PAH) has an identifiable genetic cause in 5% of all PAH cases. Due to health benefits conferred by the early detection of PAH and the recent identification of additional PAH-associated genes, we decided to offer (extended) genetic testing to all incident and prevalent idiopathic PAH (iPAH) and pulmonary veno-occlusive disease (PVOD) patients in our clinic. Here, we report the lessons learned from (re-)contacting iPAH/PVOD patients concerning the uptake and analysis of identified PAH-associated genes and patient perspectives of the approach. METHODS: Between January 2018 and April 2020, all iPAH/PVOD patients who were not previously genetically tested (contact group) and those who tested negative on prior analysis of BMPR2 and SMAD9 variants (re-contact group) were (re-)contacted for (additional) genetic testing. RESULTS: With our approach, 58% of patients (84 out of 165) opted for genetic counselling, and a pathogenic variant was found in 12% of cases (n = 10) (re-contact group, 11%, and contact group, 13%). Eighty-six percent of participants of the survey study appreciated being (re-)contacted for genetic testing. Mild psychosocial impacts were observed. CONCLUSIONS: Our report shows the importance of (re-)contact and interest of patients (as indicated by the uptake, mild psychosocial impact and appreciation) in PAH.