Nanibaa’ A. Garrison

Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations

Pigmentation of the skin, hair, and eyes varies both within and between human populations. Identifying the genes and alleles underlying this variation has been the goal of many candidate gene and several genome-wide association studies (GWAS). Most GWAS for pigmentary traits to date have been based on subjective phenotypes using categorical scales. But skin, hair, and eye pigmentation vary continuously. Here, we seek to characterize quantitative variation in these traits objectively and accurately and to determine their genetic basis. Objective and quantitative measures of skin, hair, and eye color were made using reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes in 176 women across 313,763 SNP loci, and replication of the most significant associations was attempted in a sample of 294 European men and women from the same countries. We find that the pigmentation phenotypes are highly stratified along axes of European genetic differentiation. The country of sampling explains approximately 35% of the variation in skin pigmentation, 31% of the variation in hair pigmentation, and 40% of the variation in eye pigmentation. All three quantitative phenotypes are correlated with each other. In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the lack of major genes affecting skin and hair color variation within Europe and suggesting that not only careful phenotyping but also larger cohorts are required to understand the genetic architecture of these complex quantitative traits. Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world.

Family Ties: The Use of DNA Offender Databases to Catch Offenders' Kin

The authors examine the scientific possibility and the legal and ethical implications of using DNA forensic technology, through partial matches to DNA from crime scenes, to turn into suspects the relatives of people whose DNA profiles are in forensic databases.

A systematic literature review of individuals’ perspectives on broad consent and data sharing in the United States

Purpose:In 2011, an Advanced Notice of Proposed Rulemaking proposed that de-identified human data and specimens be included in biobanks only if patients provide consent. The National Institutes of Health Genomic Data Sharing policy went into effect in 2015, requiring broad consent from almost all research participants.Methods:We conducted a systematic literature review of attitudes toward biobanking, broad consent, and data sharing. Bibliographic databases included MEDLINE, Web of Science, EthxWeb, and GenETHX. Study screening was conducted using DistillerSR.Results:The final 48 studies included surveys (n = 23), focus groups (n = 8), mixed methods (n = 14), interviews (n = 1), and consent form analyses (n = 2). Study quality was characterized as good (n = 19), fair (n = 27), and poor (n = 2). Although many participants objected, broad consent was often preferred over tiered or study-specific consent, particularly when broad consent was the only option, samples were de-identified, logistics of biobanks were communicated, and privacy was addressed. Willingness for data to be shared was high, but it was lower among individuals from under-represented minorities, individuals with privacy and confidentiality concerns, and when pharmaceutical companies had access to data.Conclusions:Additional research is needed to understand factors affecting willingness to give broad consent for biobank research and data sharing in order to address concerns to enhance acceptability.Genet Med 18 7, 663–671.

Return of results in the genomic medicine projects of the eMERGE network

The electronic Medical Records and Genomics (eMERGE) (Phase I) network was established in 2007 to further genomic discovery using biorepositories linked to the electronic health record (EHR). In Phase II, which began in 2011, genomic discovery efforts continue and in addition the network is investigating best practices for implementing genomic medicine, in particular, the return of genomic results in the EHR for use by physicians at point-of-care. To develop strategies for addressing the challenges of implementing genomic medicine in the clinical setting, the eMERGE network is conducting studies that return clinically-relevant genomic results to research participants and their health care providers. These genomic medicine pilot studies include returning individual genetic variants associated with disease susceptibility or drug response, as well as genetic risk scores for common “complex” disorders. Additionally, as part of a network-wide pharmacogenomics-related project, targeted resequencing of 84 pharmacogenes is being performed and select genotypes of pharmacogenetic relevance are being placed in the EHR to guide individualized drug therapy. Individual sites within the eMERGE network are exploring mechanisms to address incidental findings generated by resequencing of the 84 pharmacogenes. In this paper, we describe studies being conducted within the eMERGE network to develop best practices for integrating genomic findings into the EHR, and the challenges associated with such work.

Genomic Justice for Native Americans: Impact of the Havasupai Case on Genetic Research

In 2004, the Havasupai Tribe filed a lawsuit against the Arizona Board of Regents and Arizona State University (ASU) researchers upon discovering their DNA samples, initially collected for genetic studies on type 2 diabetes, had been used in several other genetic studies. The lawsuit reached a settlement in April 2010 that included monetary compensation and return of DNA samples to the Havasupai but left no legal precedent for researchers. Through semistructured interviews, institutional review board (IRB) chairs and human genetics researchers at US research institutions revealed their perspectives on the Havasupai lawsuit. For interviewees, the suit drew attention to indigenous concerns over genetic studies and increased their awareness of indigenous views. However, interviewees perceived no direct impact from the Havasupai case on their work; if they did, it was the perceived need to safeguard themselves by obtaining broad consent or shying away from research with indigenous communities altogether, raising important questions of justice for indigenous and minority participants. If researchers and IRBs do not change their practices in light of this case, these populations will likely continue to be excluded from a majority of research studies and left with less access to resources and potential benefit from genetic research participation.

Awareness and Acceptable Practices: IRB and Researcher Reflections on the Havasupai Lawsuit

Background: In 2003, Havasupai Tribe members in Arizona discovered that their DNA samples, collected for genetic studies on type II diabetes, had been used for studies on schizophrenia, migration, and inbreeding without their approval. The resulting lawsuit brought by the Havasupai reached a settlement in April 2010 in which tribe members received monetary compensation and the return of DNA samples. In this study, we examine the perceptions of institutional review board (IRB) chairpersons and human genetic researchers about the case and its impact on the practice of research. Methods: Twenty-minute semistructured interviews were conducted with 26 institutional review board (IRB) chairs and researchers at six top National Institutes of Health (NIH)-funded institutions. Participants were questioned about their knowledge and perceived impact of the Havasupai case and their perceptions of informed consent in genetic research studies. Results: We found that most study participants did not perceive that the Havasupai case had a large impact. However, we identified key concerns and opinions of the case, in particular, increased awareness of culturally sensitive issues with informed consent and secondary uses of samples. Conclusions: The results provide a deeper understanding of how informed consent issues are understood by IRB members and human genetic researchers and the implications for research ethics education.

Customers or research participants?: Guidance for research practices in commercialization of personal genomics

Genet Med 2012:14(10):833–835

Advancing the ethics of paleogenomics

Ancestral remains should be regarded not as “artifacts” but as human relatives who deserve respect Recent scientific developments have drawn renewed attention to the complex relationships among Indigenous peoples, the scientific community, settler colonial governments, and ancient human remains (1, 2). Increasingly, DNA testing of ancestral remains uncovered in the America s is being used in disputes over these remains (3). However, articulations of ethical principles and practices in paleogenomics have not kept pace (4), even as results of these studies can have negative consequences, undermining or complicating community claims in treaty, repatriation, territorial, or other legal cases. Paleogenomic narratives may also misconstrue or contradict community histories, potentially harming community or individual identities. Paleogenomic data can reveal information about descendant communities that may be stigmatizing, such as genetic susceptibilities to disease. Given the potential consequences for Indigenous communities, it is critical that paleogenomic researchers consider their ethical obligations more carefully than in the past.

Creating a data resource: what will it take to build a medical information commons?

National and international public–private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is widely available for both research and clinical uses. Stakeholder participation is essential in clarifying goals, deepening understanding of areas of complexity, and addressing long-standing policy concerns such as privacy and security and data ownership. This article describes eight core principles proposed by a diverse group of expert stakeholders to guide the formation of a successful, sustainable MIC. These principles promote formation of an ethically sound, inclusive, participant-centric MIC and provide a framework for advancing the policy response to data-sharing opportunities and challenges.

Trust, Precision Medicine Research, and Equitable Participation of Underserved Populations

Through the use of culturally appropriate videos on precision medicine research (PMR) that were developed and tailored to five racial and ethnic groups of patients, and subsequent focus-group discu...