Informed consent for forensic genetic population studies: Status quo and a call for harmonization

Martin Bodner, Walther Parson

Forensic Science International: Genetics, June 2025

Abstract

Donor-signed informed consent is a fundamental prerequisite for ethically correct analysis and publication of genetic data in forensic population studies, including quality assessment of datasets and their inclusion into frequency databases. While considerations on the requirement and content of informed consent have been published, little information is available with regard to the actual nature of the documents currently in use. This study investigated 50 recent informed consent forms submitted to EMPOP and STRidER from a broad range of contributors across worldwide legislations, irrespective of the quality of the associated genetic data. The common ground of the informed consent forms, their specific content and differences, and the extent to which they contain suggested components are outlined. This evaluation of authentic informed consent form diversity adds to the discussion on formal aspects to be covered at the time of sampling and may expedite future harmonization of informed consent in forensic population studies, assuring ethical principles in the application of precious sample sets for a broad range of investigations across genetic disciplines.

Health system-led early consent and direct contact of at-risk relatives: Pilot study results
Nora B Henrikson, Aaron Scrol, Jamilyn M Zepp, Melissa L Anderson, Paula R Blasi, John J Ewing, Jane Grafton, James D Ralston, Stephanie M Fullerton, Kathleen A Leppig
Public Health Genomics, 3 April 2025
Abstract
Introduction
At-risk relatives of probands with genetic variants associated with hereditary cancer risk should receive cascade genetic testing. In the U.S., probands are expected to notify their own at-risk relatives, but many relatives never learn of their risk, representing missed opportunity to reduce morbidity and mortality associated with hereditary cancers. Direct contact of relatives could reach relatives not contacted by the proband. We conducted a single-arm, prospective pilot evaluation of a direct contact intervention based on patient and family preferences. Here we report the study’s quantitative results, measured by proband and relative participation in the intervention follow-up survey.
Methods
We recruited adults receiving genetic counseling for inherited cancer risk at one U.S. integrated health system. A genetic counselor offered to contact at-risk relatives. We surveyed probands and relatives at study enrollment and 6-8 weeks and evaluated administrative data to assess the program’s outreach to probands and relatives, its acceptability, and its limited efficacy.
Results
We approached 148 probands before their genetic counseling appointment. 55 (37%) consented to study participation. Of these, 31 completed genetic testing, 29 of whom provided consent to contact 101 relatives. 44% (n=45) of relatives consented to be contacted by the study genetic counselor. Acceptability was high for both groups and no harms were reported. All relatives reached (n=43) received their proband’s test results, including 6 pathogenic/likely pathogenic findings.
Conclusion
A direct contact program was acceptable, reached at-risk relatives and communicated proband test results. Direct contact with early consent of relatives holds promise for future research.

Editor’s Note: Our Center is examining the nuanced underlying issues raised by this important article.

Consent for genomic sequencing: a conversation, not just a form
Comment
Danya F. Vears
European Journal of Human Genetics, 3 March 2025
Open Access
Excerpt
How to obtain truly informed consent for genomic sequencing in clinical practice is a long-standing topic of debate in the field. Although some research (including interviews with health professionals and analysis of consent forms) has already been conducted in this space, these studies can often only give a vague indication of the nature of the information that patients or families might be provided. They are limited in that they assume that health professionals use the consent form as a template to guide the discussion with the patient when, in reality, very little research has been conducted that examines exactly how, if at all, consent forms are utilised in these consultations. The study conducted by Ellard et al. [1] goes a step further than most to explore what happens during a consent interaction when patients are offered diagnostic genomic sequencing within a public health service. Their team audio-recorded consent conversations between healthcare professionals and parents of paediatric patients offered WGS through the Genomic Medicine Service across seven regionally diverse NHS Trusts in the United Kingdom. However, it also raises further questions, including how to make a consent interaction into a legitimate conversation and what information is important to convey during this conversation…

Analysis of informed consent forms of patients undergoing cancer genetic testing in the era of next-generation sequencing
Research
Tina Kerševan, Tina Kogovšek, Ana Blatnik, Mateja Krajc
Hereditary Cancer in Clinical Practice, 21 February 2025
Open Access
Abstract
Background
The Department of Clinical Cancer Genetics at the Institute of Oncology Ljubljana offers genetic counselling and testing to cancer patients and their relatives. Before undergoing genetic testing, patients sign the informed consent form. In addition to giving consent for collection of biological material and genetic testing, patients decide about storage of biological material and participation in international databases. Furthermore, patients decide whether the information regarding their test results may be revealed to their blood relatives and whether they want to be informed about secondary findings.
Methods
Using the signed consent forms, we investigated the effect of selected factors on patients’ decisions. Using different statistical methods, we tried to determine the proportion of patients who opted for different items and the effect of gender, age and cancer diagnoses on their decisions.
Results
Nearly all (99.6%) patients, regardless of gender, age, and presence of oncological diagnosis, consented to the storage of their biological material, 98.4% of patients, regardless of gender, age, and presence of oncological diagnosis, wanted to be included in international databases in a pseudo-anonymised form, 98.8% of patients, irrespective of gender, age, and presence of oncological diagnosis, allowed blood relatives to see their results, and 98.4% of patients, irrespective of gender, age and presence of oncological diagnosis, wanted to know whether secondary findings were detected when genetic analysis of their biological material was performed. Men are, on average, more likely to consent but the difference between genders is not statistically significant. Patients without oncological disease were more likely to agree to be included in international databases than patients with a confirmed oncological diagnosis.
Conclusions
Our results show that the vast majority of patients were in favour of the options they were offered. Most importantly, the majority of them allow their genetic test results be revealed to their blood relatives when needed and would participate in international databases. Research in rare diseases, including rare cancer genetic predisposition syndromes, is crucial for optimal diagnostic, prevention and treatment options for patients with rare genetic disorders. The results are also important for refining the approach to pre-and post-test cancer genetic counselling.

New Online Consent Tool for Patients
Australian Genomics, 23 January 2025
Abstract
Informed consent is a critical component of genomic and genetic testing. It is a process whereby a patient agrees to undergo genomic testing in full knowledge of the potential risks, benefits and outcomes. It is therefore essential that they are given clear and transparent information to support their decision. A new interactive online tool developed by Australian Genomics provides easy and accessible information in bite-sized chunks to guide patients through the key concepts of genomic testing. It is designed to complement the updated genetic and genomic clinical consent package released by Australian Genomics earlier last year. “These consent materials are among the most popular resources we have produced,” said Project Lead Professor Julie McGaughran. “This is another step forward in our work to provide accurate and engaging material to help people better understand the often-complex process of genomic testing.” The tool is designed to provide key details upfront and then options for users to explore more information based on their interests.

Looking Beyond the IRB
Editorial
Quinn Waeiss, Margaret Levi, Leif Wenar, David Magnus
The American Journal of Bioethics, 29 January 2025
Excerpt
…Looking to the informed consent process to address group harms also brings serious complications. The first is defining the groups that could experience harm. Without careful thought to the identification of these groups, researchers run the risk of using social groups as inappropriate proxies for the groups actually under study—and those ultimately at risk of harm (Juengst Citation1998). Blanket calls for community engagement in data-centric research without careful consideration of the communities in question seems likely to reinforce the incorrect use of population descriptors in fields like genomics. Doerr and Meeder (Citation2025) highlight several additional complexities with appropriately demarcating groups in data-intensive research, including groups that researchers can analyze into existence. Even if groups are properly identified, we still need to consider the additional burdens placed on communities and their members through community engagement in the research process, and how burdens could compound if such engagement were mandatory…

Consideration and Disclosure of Group Risks in Genomics and Other Data-Centric Research: Does the Common Rule Need Revision?
Target Article
Carolyn Riley Chapman, Gwendolyn P. Quinn, Heini M. Natri, Courtney Berrios, Patrick Dwyer, Kellie Owens, Síofra Heratyf Birkbeck, Arthur L. Caplan
The American Journal of Bioethics, 2025
Abstract
Harms and risks to groups and third-parties can be significant in the context of research, particularly in data-centric studies involving genomic, artificial intelligence, and/or machine learning technologies. This article explores whether and how United States federal regulations should be adapted to better align with current ethical thinking and protect group interests. Three aspects of the Common Rule deserve attention and reconsideration with respect to group interests: institutional review board (IRB) assessment of the risks/benefits of research; disclosure requirements in the informed consent process; and criteria for waivers of informed consent. In accordance with respect for persons and communities, investigators and IRBs should systematically consider potential group harm when designing and reviewing protocols, respectively. Research participants should be informed about any potential group harm in the consent process. We call for additional public discussion, empirical research, and normative analysis on these issues to determine the right regulatory and policy path forward.

Beyond Individual Consent: The Hidden Crisis of Group Harm in the AI and Genomics Era
Open Peer Commentaries
Tony Yang
The American Journal of Bioethics, 29 January 2025
Excerpt
…Chapman and colleagues’ analysis highlights critical gaps in current regulatory frameworks, particularly around institutional review board (IRB) assessment of group risks, informed consent requirements, and criteria for consent waivers. Their work connects to and builds upon several themes identified in earlier work: the increasing salience of group risks in data-centric research, as highlighted by analyses of algorithmic harm and bias in big health data research (Obermeyer et al. Citation2019); the challenges of prospectively identifying group harms, emphasized in studies of genetic research with Indigenous communities (Garrison et al. Citation2019); and the limitations of individual-focused protections in addressing collective risks, a theme present across multiple analyses…

What does a consent conversation for whole genome sequencing look like in the NHS Genomic Medicine Service? An observational study
Holly Ellard, Huda Alfardus, Saskia Sanderson, Celine Lewis
European Journal Of Human Genetics, 26 November 2024
Open Access
Abstract
Patient choice consent for whole genome sequencing (WGS) through the Genomic Medicine Service in England covers consent to diagnostic testing and an invitation to the National Genomic Research Library (NGRL). Little is known about what consent conversations for WGS look like in practice. We audio-recorded and analysed the content and structure of consent appointments (n = 26) between healthcare professionals (HCPs) and parents of children with rare disease across seven NHS Trusts. Appointments frequently covered the potential findings from testing, implications for family members, and DNA storage, but often omitted that data may be reanalysed in the future if a diagnosis is not made. Consent to the NGRL was typically sought during the same appointment; these discussions varied in content, but frequently included a background to the NGRL and data security. HCPs often tempered expectations around what WGS can achieve and asked questions to clarify parents’ understanding, but less commonly elicited parents’ values and concerns. Administrative tasks were time-consuming, but took less time when consent was recorded digitally. Future training should emphasise how to elicit patients’ values and concerns. Digital infrastructure and hiring roles such as genomic associates to support consent may be important strategies to meet the workload demands of WGS.

Variance of Consent for Genetic Return of Results Across Sociodemographic Traits
Christine Jovanovic, Brynn Mayer
University of Illinois Library, 25 November 2024
Abstract
There is a gap in the literature assessing whether demographic variables are associated with uptake of genetic testing in the absence of identified barriers of referral and cost. Because the All of Us Research Program offers genetic testing and counseling at no cost, we propose to address this gap using data from the University of Illinois Chicago All of Us Research Program, which includes over 16,000 individuals. This study will aim to assess whether consent to receive genetic return of results (GRoR) varies significantly across relevant sociodemographic factors among the diverse participants in the University of Illinois Chicago (UIC) All of Us cohort.