title: Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry.
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.
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kessler
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Yerges-Armstrong
authors.affiliation: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Taub
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Amol C
authors.initials: AC
authors.lastname: Shetty
authors.affiliation: Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Maloney
authors.affiliation: Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Linda Jo Bone
authors.initials: LJB
authors.lastname: Jeng
authors.affiliation: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan 48202, USA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Levin
authors.affiliation: Center for Health Policy &Health Services Research, Henry Ford Health System, Detroit, Michigan 48202, USA.|Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan 48202, USA.
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.|Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21224, USA.
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.|Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21224, USA.|Department of Medicine, University of Colorado, Aurora, Colorado 80045, USA.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Connor
mesh_terms: D015982:Bias; D044383:Black People / Q000235:genetics*; D014644:Genetic Variation; D023281:Genomics; D054625:Healthcare Disparities; D006801:Humans; D058977:Molecular Sequence Annotation; D057285:Precision Medicine; D013997:Time Factors