Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry
Authors: Kessler Michael D. , Yerges-Armstrong Laura , Taub Margaret A. , Shetty Amol C. , Maloney Kristin , Jeng Linda Jo Bone , Ruczinski Ingo , Levin Albert M. , Williams L. Keoki , Beaty Terri H. , Mathias Rasika A. , Barnes Kathleen C. ,   Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA), Boorgula Meher Preethi , Campbell Monica , Chavan Sameer , Ford Jean G. , Foster Cassandra , Gao Li , Hansel Nadia N. , Horowitz Edward , Huang Lili , Ortiz Romina , Potee Joseph , Rafaels Nicholas , Scott Alan F. , Vergara Candelaria , Gao Jingjing , Hu Yijuan , Johnston Henry Richard , Qin Zhaohui S. , Padhukasahasram Badri , Dunston Georgia M. , Faruque Mezbah U. , Kenny Eimear E. , Gietzen Kimberly , Hansen Mark , Genuario Rob , Bullis Dave , Lawley Cindy , Deshpande Aniket , Grus Wendy E. , Locke Devin P. , Foreman Marilyn G. , Avila Pedro C. , Grammer Leslie , Kim Kwang-YounA , Kumar Rajesh , Schleimer Robert , Bustamante Carlos , De La Vega Francisco M. , Gignoux Chris R. , Shringarpure Suyash S. , Musharoff Shaila , Wojcik Genevieve , Burchard Esteban G. , Eng Celeste , Gourraud Pierre-Antoine , Hernandez Ryan D. , Lizee Antoine , Pino-Yanes Maria , Torgerson Dara G. , Szpiech Zachary A. , Torres Raul , Nicolae Dan L. , Ober Carole , Olopade Christopher O. , Olopade Olufunmilayo , Oluwole Oluwafemi , Arinola Ganiyu , Song Wei , Abecasis Goncalo , Correa Adolfo , Musani Solomon , Wilson James G. , Lange Leslie A. , Akey Joshua , Bamshad Michael , Chong Jessica , Fu Wenqing , Nickerson Deborah , Reiner Alexander , Hartert Tina , Ware Lorraine B. , Bleecker Eugene , Meyers Deborah , Ortega Victor E. , Pissamai Maul R. N. , Trevor Maul R. N. , Watson Harold , Araujo Maria Ilma , Oliveira Ricardo Riccio , Caraballo Luis , Marrugo Javier , Martinez Beatriz , Meza Catherine , Ayestas Gerardo , Herrera-Paz Edwin Francisco , Landaverde-Torres Pamela , Erazo Said Omar Leiva , Martinez Rosella , Mayorga Alvaro , Mayorga Luis F. , Mejia-Mejia Delmy-Aracely , Ramos Hector , Saenz Allan , Varela Gloria , Vasquez Olga Marina , Ferguson Trevor , Knight-Madden Jennifer , Samms-Vaughan Maureen , Wilks Rainford J. , Adegnika Akim , Ateba-Ngoa Ulysse , Yazdanbakhsh Maria , O’Connor Timothy D. 
Published: October 2016

AbstractTo 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.