Investigative genetic genealogy practices warranting policy attention: Results of a modified policy Delphi.

A technique known as investigative genetic genealogy (IGG) was first introduced to criminal investigations in 2018, and it has since been used by U.S. law enforcement to help identify hundreds of criminal perpetrators and unidentified human remains.

Applying health equity implementation science frameworks to population genetic screening.

Introduction: Implementation science frameworks with a focus on health equity have emerged to help guide the introduction of new interventions into healthcare and community settings while limiting health disparities. The purpose of this research was to explore the applicability of such frameworks to guide the equitable implementation of population genetic screening programs.

Methods: We searched PubMed and reference lists for relevant frameworks and examples of their use in health settings.

"I Didn't Have to Worry about It": Patient and Family Experiences with Health System Involvement in Notifying Relatives of Genetic Test Results.

Introduction: In the USA, patients who undergo genetic testing for hereditary cancer risk are responsible for informing relatives about their genetic test results, but many relatives never find out they might be at risk. A health system-mediated relative notification program might help fill this gap, but questions remain about the acceptability of this approach.

Methods: We analyzed qualitative data from a single-arm, nonrandomized, mixed-methods study to understand how patients and families experienced a new health system-mediated relative notification program.

Policy and laboratory practice: How quality control procedures for genetic testing perpetuate biological essentialism and discrimination against transgender, gender diverse, and intersex people.

Transgender, gender diverse, and intersex (TGDI) individuals face significant health disparities due to individual and systemic experiences of discrimination, impacting their access to healthcare. While clinical genetic testing has become increasingly accessible to the general population, the field of clinical genetics perpetuates a narrative of biological essentialism, which creates barriers for TGDI patients. Biological essentialism upholds that sex is a binary, fixed, and innate characteristic, a misconception that has been historically weaponized against the TGDI community in both individual experiences of discrimination and anti-trans legislation, among other systemic forms of oppression.

Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network.

The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

Background: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating.

Public Perspectives on Investigative Genetic Genealogy: Findings from a National Focus Group Study.

Background: Investigative genetic genealogy (IGG) is a technique that involves uploading genotypes developed from perpetrator DNA left at a crime scene, or DNA from unidentified remains, to public genetic genealogy databases to identify genetic relatives and, through the creation of a family tree, the individual who was the source of the DNA. As policymakers demonstrate interest in regulating IGG, it is important to understand public perspectives on IGG to determine whether proposed policies are aligned with public attitudes.

Methods: We conducted eight focus groups with members of the public ( = 72), sampled from four geographically diverse US regions, to explore general attitudes and perspectives regarding aspects of IGG practices, applications, and policies.

IGG in the trenches: Results of an in-depth interview study on the practice, politics, and future of investigative genetic genealogy.

Investigative genetic genealogy (IGG) is a new technique for identifying criminal suspects and unidentified deceased and living persons that has sparked controversy. In a criminal case, the technique involves uploading genetic information left by a putative perpetrator at the crime scene to one or more direct-to-consumer genetic genealogy databases with the intention of identifying the perpetrator's genetic relatives and, eventually, locating the perpetrator on the family tree. In 2018, IGG helped to identify the Golden State Killer, and it has since been used in hundreds of investigations in the United States.

Interrogating the Value of Return of Results for Diverse Populations: Perspectives from Precision Medicine Researchers.

Background: Over the last decade, the return of results (ROR) in precision medicine research (PMR) has become increasingly routine. Calls for individual rights to research results have extended the "duty to report" from clinically useful genetic information to traits and ancestry results. ROR has thus been reframed as inherently beneficial to research participants, without a needed focus on who benefits and how.

Conflating race and ancestry: Tracing decision points about population descriptors over the precision medicine research life course.

Responding to calls for human genomics to shift away from the use of race, genomic investigators are coalescing around the possibility of using genetic ancestry. This shift has renewed questions about the use of social and genetic concepts of difference in precision medicine research (PMR). Drawing from qualitative data on five PMR projects, we illustrate negotiations within and between research teams as genomic investigators deliberate on the relevance of race and genetic ancestry for different analyses and contexts.

An Ethical Framework for Research Using Genetic Ancestry.

A wide range of research uses patterns of genetic variation to infer genetic similarity between individuals, typically referred to as genetic ancestry. This research includes inference of human demographic history, understanding the genetic architecture of traits, and predicting disease risk. Researchers are not just structuring an intellectual inquiry when using genetic ancestry, they are also creating analytical frameworks with broader societal ramifications.

Factors Influencing Genetic Screening Enrollment among a Diverse, Community-Ascertained Cohort.

Introduction: Genetic screening for preventable adult-onset hereditary conditions has been proposed as a mechanism to reduce health disparities. Analysis of how race and ethnicity influence decision-making to receive screening can inform recruitment efforts and more equitable population screening design. A study at the University of Washington Medicine that invited unselected patients to participate in genetic screening for pathogenic variation in medically important genes provided an opportunity to evaluate these factors.

Critical assessment of variant prioritization methods for rare disease diagnosis within the Rare Genomes Project.

Background: A major obstacle faced by rare disease families is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years, and causal variants are identified in under 50%. The Rare Genomes Project (RGP) is a direct-to-participant research study on the utility of genome sequencing (GS) for diagnosis and gene discovery.

Studying the impact of translational genomic research: Lessons from eMERGE.

Two major goals of the Electronic Medical Record and Genomics (eMERGE) Network are to learn how best to return research results to patient/participants and the clinicians who care for them and also to assess the impact of placing these results in clinical care. Yet since its inception, the Network has confronted a host of challenges in achieving these goals, many of which had ethical, legal, or social implications (ELSIs) that required consideration. Here, we share impediments we encountered in recruiting participants, returning results, and assessing their impact, all of which affected our ability to achieve the goals of eMERGE, as well as the steps we took to attempt to address these obstacles.

Cloud-based biomedical data storage and analysis for genomic research: Landscape analysis of data governance in emerging NIH-supported platforms.

The storage, sharing, and analysis of genomic data poses technical and logistical challenges that have precipitated the development of cloud-based computing platforms designed to facilitate collaboration and maximize the scientific utility of data. To understand cloud platforms' policies and procedures and the implications for different stakeholder groups, in summer 2021, we reviewed publicly available documents (N = 94) sourced from platform websites, scientific literature, and lay media for five NIH-funded cloud platforms (the All of Us Research Hub, NHGRI AnVIL, NHLBI BioData Catalyst, NCI Genomic Data Commons, and the Kids First Data Resource Center) and a pre-existing data sharing mechanism, dbGaP. Platform policies were compared across seven categories of data governance: data submission, data ingestion, user authentication and authorization, data security, data access, auditing, and sanctions.

Community Engagement in Precision Medicine Research: Organizational Practices and Their Impacts for Equity.

Background: In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal.

Methods: Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for.

Results: We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant consequences for the time and resources devoted to engagement and the ultimate impacts it has on research.

Diagnostic yield of genetic screening in a diverse, community-ascertained cohort.

Background: Population screening for genetic risk of adult-onset preventable conditions has been proposed as an attractive public health intervention. Screening unselected individuals can identify many individuals who will not be identified through current genetic testing guidelines.

Methods: We sought to evaluate enrollment in and diagnostic yield of population genetic screening in a resource-limited setting among a diverse population.