Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry

Michael D. Kessler; Laura Yerges-Armstrong; Margaret A. Taub; Amol C. Shetty; Kristin Maloney; Linda Jo Bone Jeng; Ingo Ruczinski; Albert M. Levin; L. Keoki Williams; Terri H. Beaty; Rasika A. Mathias; Kathleen C. Barnes; Timothy D. O'Connor

doi:10.1038/ncomms12521

Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry

Michael D. Kessler, Laura Yerges-Armstrong, Margaret A. Taub, Amol C. Shetty, Kristin Maloney, Linda Jo Bone Jeng, Ingo Ruczinski, Albert M. Levin, L. Keoki Williams, Terri H. Beaty, Rasika A. Mathias, Kathleen C. Barnes, Timothy D. O'Connor

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVar's correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=-0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations.

Original language	English (US)
Article number	12521
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12521
State	Published - Oct 11 2016

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Kessler, M. D., Yerges-Armstrong, L., Taub, M. A., Shetty, A. C., Maloney, K., Jeng, L. J. B., Ruczinski, I., Levin, A. M., Williams, L. K., Beaty, T. H., Mathias, R. A., Barnes, K. C., & O'Connor, T. D. (2016). Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry. Nature communications, 7, Article 12521. https://doi.org/10.1038/ncomms12521

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abstract = "To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVar's correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=-0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations.",

author = "Kessler, {Michael D.} and Laura Yerges-Armstrong and Taub, {Margaret A.} and Shetty, {Amol C.} and Kristin Maloney and Jeng, {Linda Jo Bone} and Ingo Ruczinski and Levin, {Albert M.} and Williams, {L. Keoki} and Beaty, {Terri H.} and Mathias, {Rasika A.} and Barnes, {Kathleen C.} and O'Connor, {Timothy D.}",

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AU - Maloney, Kristin

AU - Jeng, Linda Jo Bone

AU - Ruczinski, Ingo

AU - Levin, Albert M.

AU - Williams, L. Keoki

AU - Beaty, Terri H.

AU - Mathias, Rasika A.

AU - Barnes, Kathleen C.

AU - O'Connor, Timothy D.

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Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry

Abstract

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