Abstract Circulating plasma proteins are key biomarkers and therapeutic targets, now measurable at scale through high-throughput technologies, yet whether expanding proteomics platforms beyond the classical plasma secretome enhances genetic discovery and causal inference remains poorly understood. Here, we use an expanded SomaScan 7k platform to map the genetic architecture of a broader segment of the plasma proteome and to evaluate how proteome expansion affects pQTL discovery, causal inference and therapeutic target prioritisation. After quality control, we analysed 7,144 aptamers targeting 6,267 proteins in the harmonised dataset of two European cohorts: INTERVAL (n = 9,251 participants) and CHRIS (n = 4,194), and conducted genome-wide pQTL association analyses followed by meta-analysis. We identified 7,870 significant pQTLs (P-value < 1.26 × 10 −11 ; 1,784 cis , 6,086 trans ), of which 2,704 (34%) associations were not reported in five prior large-scale pQTL studies. Newly assessed proteins, which accounted for 53% (1,422/2,704) of the novel associations, were less likely to harbour cis -pQTLs associations (∼15%) than those in the previous platform version (∼28%), consistent with their lower expected plasma concentrations and predominantly intracellular localisation. Colocalization analyses revealed widespread sharing of genetic signals across proteins and characterised 22 pleiotropic trans -regulatory hotspots accounting for 68% of all trans -pQTLs. Through two-sample Mendelian randomization analyses on 2,003 phenotypes from the Million Veteran Program, UK Biobank, and FinnGen (combined N > 1.2 million), we identified 6,340 genetically supported protein–trait associations, highlighting disease mechanisms and potential therapeutic opportunities beyond currently drug-targeted circulating proteins. Together, these findings provide a systematic view of the genetic architecture of the expanded plasma proteome and demonstrate that plasma proteome expansion reveals genetically anchored disease biology beyond the classical secretome, while exposing inherent biological and technical constraints of studying low-abundance intracellular proteins in circulation.

We recently established an external quality assessment (EQA) scheme for next-generation sequencing (NGS) diagnostics in rare neurological disorders (RND) in collaboration with the EMQN. The first assessment rounds revealed limitations and variability in the quality and completeness of genetic testing reports. To improve and harmonize reporting in NGS-based diagnostics for RND, we identified 28 topics requiring recommendations based on EQA findings. These topics were grouped into four areas: clinical information, interpretation, methodology, and reporting. A team of 31 experts with relevant expertise was formed. Using an adapted Delphi approach, two rounds of surveys were conducted to prioritize the topics. Subsequently, area-specific expert groups met to formulate recommendations, followed by a final approval round using the five-finger consensus method involving all experts. In both Delphi rounds, all topics were rated as either very important (n = 12) or important (n = 16), and all were advanced for recommendation development. Consensus recommendations were achieved for 27 of the 28 topics. These include guidance on gene panel composition and updating, addressing disease-specific limitations of NGS (e.g., repeat expansion disorders), defining minimal quality parameters, and promoting sharing of variant interpretations. Each recommendation is supported by real-world examples. Due to differences in national healthcare frameworks and policies, consensus could not be reached regarding which patients should or should not undergo NGS testing. The dissemination of these recommendations is expected to improve the quality of genetic testing and reporting in RND diagnostics, promoting harmonization across laboratories and enabling easier comparison and interpretation of genetic testing reports.

This study examines the complex and often ambiguous conceptualization of consent in European health research, focusing on the relationship between informed consent to participate in research and consent as a legal basis for personal data processing. Differences between these two forms of consent may lead to inconsistent procedures and requirements, thereby generating legal and practical challenges for researchers, ethics committees, data protection authorities, and other oversight bodies. Drawing on two use cases involving observational retrospective studies, the paper compares consent requirements and oversight practices in Belgium, the Czech Republic, Finland, France, Germany, Italy, Poland, and Spain, highlighting persistent fragmentation and uneven institutional coordination across national research governance systems. The paper also distinguishes between 'monist' conceptions of consent, which view research and data protection consent as expressions of a single normative concept, and 'dualist' conceptions, which treat them as distinct forms of authorization grounded in different ethical and legal rationales. The paper concludes by reflecting on the implications of the upcoming European Health Data Space Regulation, arguing that its approach to secondary data use may further accentuate existing tensions and highlighting the need for greater conceptual clarity and institutional coordination in European health research governance.

As genomics infrastructure expands, current governance will determine whether it advances global health equity or entrenches disparities, locking biased data into future clinical tools. This Comment calls for inclusive, community-centered genomic systems, before biased data and extractive models becoming the default.

Human DNA is unavoidably present in metagenomic analyses of human microbiomes. While current protocols remove human DNA before submission to public repositories, mitochondrial DNA (mtDNA) has been overlooked and frequently persists. We discuss the privacy risks and research opportunities associated with mtDNA, urging consideration by the scientific, ethics, and legal communities.

Precision medicine and artificial intelligence (AI) are increasingly integrated into colorectal cancer (CRC) care, offering personalised treatment strategies and data-driven decision support. While these technologies promise improved outcomes, they also raise challenges concerning clinical decision-making, the doctor-patient relationship, and ethics. This study explores physicians’ perspectives on integrating precision medicine and AI in CRC care. A qualitative study was conducted using semi-structured interviews with ten CRC physicians from six European countries. Participants were recruited through purposive and snowball sampling. Interviews were analysed using thematic analysis. Three key themes emerged from the analysis. First, physicians described precision medicine as a logical extension of existing tailoring practices, offering new opportunities while introducing complexity. Many expressed concerns about the blurred boundary between experimental and standard treatments, noting potential implications for equity and ethical decision-making. Second, AI was viewed as a future partner in care, with the potential to enhance efficiency and assist in synthesising complex data. However, participants voiced concerns about trust, clinical responsibility, and the lack of regulatory clarity, particularly due to AI’s “black box” nature. Finally, doctors reported challenges in communicating both precision medicine and AI-based recommendations to patients. They emphasised the importance of adapting communication strategies to individual patients and highlighted the need for structured approaches to ensure patient understanding and prevent miscommunication, especially when dealing with uncertain outcomes or emerging technologies. The findings highlight both the opportunities and challenges of integrating precision medicine and AI in CRC care. Addressing concerns related to communication, ethics, and regulation requires clear guidance and improved support for clinicians. Precision medicine and AI enhance CRC care but demand robust communication, regulation, and ethical safeguards to ensure transparency, trust, and physician autonomy.

Excessive or improper lighting can affect human health and well-being. However, lighting is seldom considered within frameworks analyzing the interrelations between the urban environment and the health and well-being of communities. Lighting-related concerns are often conceptualized and discussed in environmental terms through the light pollution frame. Positively, this frame emphasizes human responsibility for the environmental detriment and animal harm caused by lighting and promotes the discussion of aesthetics and existential dimensions connected to nocturnal darkness. Negatively, it is flawed with epistemological shortcomings and normativity; it is prone to the risk of ideological and political polarisation and tends to underemphasize the health implications of excessive and improper lighting. This study addresses this gap by arguing for the advantages of a public health framing of lighting-related concerns. In particular, it highlights how this perspective can better capture the health implications of lighting and inform urban policies. Placing light concerns within a public health framework entails presenting a relatively known landscape that resonates with the value systems of virtually everyone. This approach supports the creation of a common, multi-stakeholder space in discussions on lighting policies, balancing considerations of urban security, safety, inclusivity, and accessibility as different dimensions of diverse populations’ health and well-being. By emphasizing the public health dimension, this study contributes to the discourse on lighting as a determinant of health and well-being. Such a holistic framework aligns with the United Nations Sustainable Development Goal 3 on good health and well-being by fostering conditions that advance health for all, addressing lighting not merely as an environmental issue but as a critical public health priority.

During the COVID -19 pandemic, government-to-business (G2B) data sharing became a vital practice, exemplified by the 2021 Israeli Ministry of Health-Pfizer agreement. This established a large-scale data sharing operation outside of research and data protection regulations and oversight. This paper explores two related questions: (i) whether an EU Member State could replicate this scenario, and (ii) whether EU data legislation provides sufficient protection against excessive G2B data sharing. The analysis of the General Data Protection Regulation, Data Governance Act, and European Health Data Space shows that (i) despite the uncertain definitions of research and personal data, it would be difficult for an EU Member State to replicate this scenario; and (ii) despite its many grey areas and flexibilities, EU data legislation offers protection against excessive G2B data sharing. This highlights the need to explore alternative strategies to facilitate data sharing that can address public health emergencies promptly while safeguarding fundamental rights.

Recall-by-genotype (RbG) is a bottom-up approach using existing genetic data to design follow-up stratified studies. Genetic information may be partially disclosed at invitation, thus raising ethical issues which call for defined best practices for disclosure and communication in RbG approaches. Within the context of the ProtectMove sub-project of the Cooperative Health Research in South Tyrol (CHRIS) study, we investigated research participant perspectives on RbG communication strategies (Step 1 and 4, questionnaire with a subsample of CHRIS participants with and without previous experience of RbG, respectively). Additionally, we explored researchers’ and study personnel’s experience with RbG (Step 2 and 3, focus group discussion). In step 1 (N = 95), participants were generally satisfied with the study process. Most (71.6

Population biobanks are an increasingly important infrastructure to support research and will be a much-needed resource in the delivery of personalised medicine. Artificial intelligence (AI) systems can process and cross-link very large amounts of data quickly and be used not only for improving research power but also for helping with complex diagnosis and prediction of diseases based on health profiles. AI, therefore, potentially has a critical role to play in personalised medicine, and biobanks can provide a lot of the necessary baseline data related to healthy populations that will enable the development of AI tools. To develop these tools, access to personal data, and in particular, sensitive data, is required. Such data could be accessed from biobanks. Biobanks are a valuable resource for research but accessing and using the data contained within such biobanks raise a host of legal, ethical, and social issues (ELSI). This includes the appropriate consent to manage the collection, storage, use, and sharing of samples and data, and appropriate governance models that provide oversight of secondary use of samples and data. Biobanks have developed new consent models and governance tools to enable access that address some of these ELSI-related issues. In this paper, we consider whether such governance frameworks can enable access to biobank data to develop AI. As Italy has one of the most restrictive regulatory frameworks on the use of genetic data in Europe, we examine the regulatory framework in Italy. We also look at the proposed changes under the European Health Data Space (EHDS). We conclude by arguing that currently, regulatory frameworks are misaligned and unless addressed, accessing data within Italian biobanks to train AI will be severely limited.

Governance infrastructures streamline scientific and ethical provenance verification of human pluripotent stem cell (SC) lines. Yet, scientific developments (e.g., SC-derived embryo models, organoids) challenge research governance approaches to stored biospecimens, questioning the validity of informed consent (IC) models. Likewise, e-health platforms are driving major transformations in data processing, prompting a reappraisal of IC. Given these developments, participatory research platforms are identified as effective tools to promote longitudinal engagement, interactive decision-making, and dynamic governance. Learning from European initiatives piloting dynamic IC for biobanking and SC research, this Perspective explores the benefits and challenges of implementing dynamic IC and governance for SC.

The COVID-19 pandemic demonstrated the benefits of international data sharing. Data sharing enabled the health care policy makers to make decisions based on real-time data, it enabled the tracking of the virus, and importantly it enabled the development of vaccines that were crucial to mitigating the impact of the virus. This data sharing is not the norm as data sharing needs to navigate complex ethical and legal rules, and in particular, the fragmented application of the General Data Protection Regulation (GDPR). The introduction of the draft regulation for a European Health Data Space (EHDS) in May 2022 seeks to address some of these legal issues. If passed, it will create an obligation to share electronic health data for certain secondary purposes. While there is a clear need to address the legal complexities involved with data sharing, it is critical that any proposed reforms are in line with ethical principles and the expectations of the data subjects. In this paper we offer a critique of the EHDS and offer some recommendations for this evolving regulatory space.

This paper discusses the importance of return of clinical trial data to patients in the context of the FACILITATE project that aims to develop a participant-centric approach for the systematic return of individual clinical trial data. It reflects on the need for an ethical framework to support the return of clinical trial data. The discussion revolves around the developing FACILITATE ethical framework, specifically focusing on the ethical principles that form the foundation of the framework and guidance on how to implement those principles into practice.

BackgroundWith new technologies, health data can be collected in a variety of different clinical, research, and public health contexts, and then can be used for a range of new purposes. Establishing the public’s views about digital health data sharing is essential for policy makers to develop effective harmonization initiatives for digital health data governance at the European level. ObjectiveThis study investigated public preferences for digital health data sharing. MethodsA discrete choice experiment survey was administered to a sample of European residents in 12 European countries (Austria, Denmark, France, Germany, Iceland, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) from August 2020 to August 2021. Respondents answered whether hypothetical situations of data sharing were acceptable for them. Each hypothetical scenario was defined by 5 attributes (“data collector,” “data user,” “reason for data use,” “information on data sharing and consent,” and “availability of review process”), which had 3 to 4 attribute levels each. A latent class model was run across the whole data set and separately for different European regions (Northern, Central, and Southern Europe). Attribute relative importance was calculated for each latent class’s pooled and regional data sets. ResultsA total of 5015 completed surveys were analyzed. In general, the most important attribute for respondents was the availability of information and consent during health data sharing. In the latent class model, 4 classes of preference patterns were identified. While respondents in 2 classes strongly expressed their preferences for data sharing with opposing positions, respondents in the other 2 classes preferred not to share their data, but attribute levels of the situation could have had an impact on their preferences. Respondents generally found the following to be the most acceptable: a national authority or academic research project as the data user; being informed and asked to consent; and a review process for data transfer and use, or transfer only. On the other hand, collection of their data by a technological company and data use for commercial communication were the least acceptable. There was preference heterogeneity across Europe and within European regions. ConclusionsThis study showed the importance of transparency in data use and oversight of health-related data sharing for European respondents. Regional and intraregional preference heterogeneity for “data collector,” “data user,” “reason,” “type of consent,” and “review” calls for governance solutions that would grant data subjects the ability to control their digital health data being shared within different contexts. These results suggest that the use of data without consent will demand weighty and exceptional reasons. An interactive and dynamic informed consent model combined with oversight mechanisms may be a solution for policy initiatives aiming to harmonize health data use across Europe.

BackgroundThe implementation of precision medicine is likely to have a huge impact on clinical cancer care, while the doctor-patient relationship is a crucial aspect of cancer care that needs to be preserved. This systematic review aimed to map out perceptions and concerns regarding how the implementation of precision medicine will impact the doctor-patient relationship in cancer care so that threats against the doctor-patient relationship can be addressed.MethodsElectronic databases (Pubmed, Scopus, Web of Science, Social Science Premium Collection) were searched for articles published from January 2010 to December 2021, including qualitative, quantitative, and theoretical methods. Two reviewers completed title and abstract screening, full-text screening, and data extraction. Findings were summarized and explained using narrative synthesis.ResultsFour themes were generated from the included articles (n = 35). Providing information addresses issues of information transmission and needs, and of complex concepts such as genetics and uncertainty. Making decisions in a trustful relationship addresses opacity issues, the role of trust, and and physicians' attitude towards the role of precision medicine tools in decision-making. Managing negative reactions of non-eligible patients addresses patients' unmet expectations of precision medicine. Conflicting roles in the blurry line between clinic and research addresses issues stemming from physicians' double role as doctors and researchers.ConclusionsMany findings have previously been addressed in doctor-patient communication and clinical genetics. However, precision medicine adds complexity to these fields and further emphasizes the importance of clear communication on specific themes like the distinction between genomic and gene expression and patients' expectations about access, eligibility, effectiveness, and side effects of targeted therapies.

EDITORIAL article Front. Psychiatry, 11 January 2023Sec. Psychopharmacology Volume 13 - 2022 | https://doi.org/10.3389/fpsyt.2022.1107037

Recall-by-genotype (RbG) research recruits participants previously involved in genetic research based on their genotype. RbG enables the further study of a particular variant of interest, but in recalling participants, it risks disclosing potentially unwanted or distressing genetic information. Any RbG strategy must therefore be done in a manner that addresses the potential ethical and social issues. As part of an RbG pilot on the penetrance of Parkinson’s disease variants, we conducted an empirical mixed-method study with 51 participants of the Cooperative Health Research in South Tyrol (CHRIS) study to understand participant views on RbG research approach. Participants were disclosed the disease under investigation but not the individual variant carrier status. Results showed that participants filtered the information received through personal experience and enacted mechanisms to address the concerns raised by invitation by resorting to personal resources and the support provided by experts. While the non-disclosure of the Parkin variant carrier status was deemed acceptable, disclosing the disease under study was important for participants. Participant preferences for disclosure of the disease under investigation and the carrier status varied according to how the knowledge of individual carrier status was perceived to impact the participant’s life. This study provided insights into participant response to the RbG research approach, which are relevant for RbG policy development. A suitable communication strategy and granular options addressing preferences for invitation in the original informed consent are critical for an ethically informed RbG policy.