Is there a way to reduce the inequity in variant interpretation on the basis of ancestry?

The underrepresentation of non-European ancestry groups in current genomic databases complicates interpretation of their genetic test results, yielding a much higher prevalence of variants of uncertain significance (VUSs). Such VUS findings can frustrate the goals of genetic testing, create anxiety in patients, and lead to unnecessary medical interventions. Approaches to addressing underrepresentation of people with genetic ancestries other than European are being undertaken by broad-based recruitment efforts. However, some underrepresented groups have concerns that might preclude participation in such efforts. We describe here two initiatives aimed at meeting the needs of underrepresented ancestry groups in genomic datasets. The two communities, the Sephardi Jewish community in New York and First Peoples of Canada, have very different concerns about contributing to genomic research and datasets. Sephardi concerns focus on the possible negative effects of genetic findings on the marriage prospects of family members. Canadian Indigenous populations seek control over the research uses to which their genetic data would be put. Both cases involve targeted efforts to respond to the groups' concerns; these efforts include governance models aimed at ensuring that the data are used primarily to inform clinical test analyses and at achieving successful engagement and participation of community members. We suggest that these initiatives could provide models for other ancestral groups seeking to improve the accuracy and utility of clinical genetic testing while respecting the underlying preferences and values of community members with regard to the use of their genetic data.
Competing Interests: Declaration of interests Laura Arbour is the Project Lead for the Silent Genomes Project. Nanibaa Garrison is a member of the International Indigenous Genomics Advisory Committee for the Silent Genomes Project. Wendy Chung is on the Scientific Advisory Board for All of Us. David Zeevi is Director of Research and Development for Dor Yeshorim. The opinions expressed in this article are those of the authors. No statement in this article should be construed as an official position of the National Human Genome Research Institute, National Institutes of Health, or Department of Health and Human Services.
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