Article
Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry
Registro en:
KESSLER, M. D. et al. Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry. Nature Communications, v. 7, p. 12521, 2016.
2041-1723
10.1038/ncomms12521
Autor
Kessler, Michael D
Armstrong, Laura Yerges
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
O'Connor, Timothy D
Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA)
Resumen
Oliveira, Ricardo Riccio. Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil. Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA)
Meher Preethi Boorgula9, Monica Campbell9, Sameer Chavan9, Jean G. Ford8,11, Cassandra Foster9, Li Gao9,
Nadia N. Hansel9, Edward Horowitz9, Lili Huang9, Romina Ortiz9, Joseph Potee9, Nicholas Rafaels9, Alan F. Scott9,
Candelaria Vergara9, Jingjing Gao12, Yijuan Hu13, Henry Richard Johnston13, Zhaohui S. Qin13,
Badri Padhukasahasram6,7, GeorgiaM.Dunston14,15, Mezbah U. Faruque15, Eimear E. Kenny16,17, Kimberly Gietzen18,
Mark Hansen18, Rob Genuario18, Dave Bullis18, Cindy Lawley18, Aniket Deshpande19, Wendy E. Grus19,
Devin P. Locke19, Marilyn G. Foreman20, Pedro C. Avila21, Leslie Grammer21, Kwang-Youn A. Kim22, Rajesh
Kumar23,24, Robert Schleimer25, Carlos Bustamante16, Francisco M. De La Vega16, Chris R. Gignoux16,
Suyash S. Shringarpure16, Shaila Musharoff16, Genevieve Wojcik16, Esteban G. Burchard26,27, Celeste Eng27,
Pierre-Antoine Gourraud28, Ryan D. Hernandez26,29,30, Antoine Lizee28, Maria Pino-Yanes27,31,
Dara G. Torgerson27, Zachary A. Szpiech26, Raul Torres32, Dan L. Nicolae33,34, Carole Ober35,
Christopher O. Olopade36, Olufunmilayo I. Olopade33, Oluwafemi Oluwole33, Ganiyu Arinola37, Wei Song1,2,3,
Goncalo Abecasis38, Adolfo Correa39, Solomon Musani39, James G.Wilson40, Leslie A. Lange41, Joshua Akey42,
Michael Bamshad43, Jessica Chong43, Wenqing Fu42, Deborah Nickerson42, Alexander Reiner44, Tina Hartert45,
Lorraine B. Ware45,46, Eugene Bleecker47, Deborah Meyers47, Victor E. Ortega47, Maul R.N. Pissamai48,
Maul R.N. Trevor48, Harold Watson49,50, Maria Ilma Araujo51, Ricardo Riccio Oliveira52, Luis Caraballo53,
Javier Marrugo54, Beatriz Martinez53, Catherine Meza53, Gerardo Ayestas55, Edwin Francisco Herrera-Paz56,57,58,
Pamela Landaverde-Torres56, Said Omar Leiva Erazo56, Rosella Martinez56, Alvaro Mayorga57, Luis F. Mayorga56,
Delmy-Aracely Mejia-Mejia57,58, Hector Ramos56, Allan Saenz55, Gloria Varela55, Olga Marina Vasquez58,
Trevor Ferguson59, Jennifer Knight-Madden59, Maureen Samms-Vaughan60, Rainford J. Wilks59,
Akim Adegnika61,62,63, Ulysse Ateba-Ngoa61,62,63 & Maria Yazdanbakhsh63 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.