Kessler MD, Yerges-Armstrong L, Taub MA, Shetty AC, Maloney K, Jeng LJ, Ruczinski I, Levin AM, Williams LK, Beaty TH, Mathias RA, Barnes KC, and O'Connor TD. Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry. Nat Commun 2016; 7:12521.
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.
Medical Subject Headings
African Continental Ancestry Group; Bias; Genetic Variation; Genomics; Healthcare Disparities; Humans; Molecular Sequence Annotation; Precision Medicine; Time Factors