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

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 Yazdanbakhsh63Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-04-06T16:20:36Z No. of bitstreams: 1 Kessler MD Challenges and....pdf: 586920 bytes, checksum: 6eae557b74acb26b925513dee8afb3d3 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-04-06T17:10:08Z (GMT) No. of bitstreams: 1 Kessler MD Challenges and....pdf: 586920 bytes, checksum: 6eae557b74acb26b925513dee8afb3d3 (MD5)Made available in DSpace on 2017-04-06T17:10:08Z (GMT). No. of bitstreams: 1 Kessler MD Challenges and....pdf: 586920 bytes, checksum: 6eae557b74acb26b925513dee8afb3d3 (MD5) Previous issue date: 2016University of Maryland School of Medicine. Institute for Genome Sciences. Baltimore, Maryland, USAUniversity of Maryland School ofMedicine. Department of Medicine. Baltimore, Maryland, USA / University of Maryland School of Medicine. Baltimore, Maryland, USAJohns Hopkins University. Department of Biostatistics, Bloomberg School of Public Health. Baltimore, Maryland, USAUniversity of Maryland School of Medicine. Institute for Genome Sciences. Baltimore, Maryland, USAUniversity of Maryland School of Medicine. Baltimore, Maryland, USAUniversity of Maryland School of Medicine. Baltimore, Maryland, USAJohns Hopkins University. Department of Biostatistics, Bloomberg School of Public Health. Baltimore, Maryland, USAHenry Ford Health System. Department of Public Health Sciences. Detroit, Michigan, USAHenry Ford Health System. Center for Health Policy & Health Services Research. Detroit, Michigan, USA / Henry Ford Health System. Department of Internal Medicine. Detroit, Michigan, USAJohns Hopkins University. Department of Epidemiology, Bloomberg School of Public Health. Baltimore, Maryland, USAJohns Hopkins University. Department of Epidemiology, Bloomberg School of Public Health. Baltimore, Maryland, USA / Johns Hopkins University. Department of Medicine. Baltimore, Maryland, USAJohns Hopkins University. Department of Epidemiology, Bloomberg School of Public Health. Baltimore, Maryland, USA / Johns Hopkins University. Department of Medicine. Baltimore, Maryland, USA / University of Colorado. Department of Medicine.Aurora, Colorado, USAUniversity of Maryland School of Medicine. Institute for Genome Sciences. Baltimore, Maryland, USA / University of Maryland School ofMedicine. Department of Medicine. Baltimore, Maryland, USA / University of Maryland School of Medicine. Baltimore, Maryland, USA. Múltipla - ver em NotasTo 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

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

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\u27s 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

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Background: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. Methods: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American–specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. Results: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. Conclusions: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases. © 2022, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome

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Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations

OLIVEIRA, Ricardo Riccio. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. Michelle Daya1, Nicholas Rafaels1, Tonya M. Brunetti1, Sameer Chavan1, Albert M. Levin2, Aniket Shetty1, Christopher R. Gignoux1, Meher Preethi Boorgula1, Genevieve Wojcik 3, Monica Campbell1, Candelaria Vergara 4, Dara G. Torgerson5, Victor E. Ortega6, Ayo Doumatey7, Henry Richard Johnston8, Nathalie Acevedo9, Maria Ilma Araujo10, Pedro C. Avila 11, Gillian Belbin12, Eugene Bleecker13, Carlos Bustamante3, Luis Caraballo9, Alvaro Cruz14, Georgia M. Dunston15, Celeste Eng5, Mezbah U. Faruque16, Trevor S. Ferguson 17, Camila Figueiredo18, Jean G. Ford19, Weiniu Gan20, Pierre-Antoine Gourraud21, Nadia N. Hansel4, Ryan D. Hernandez22, Edwin Francisco Herrera-Paz 23,24, Silvia Jiménez9, Eimear E. Kenny12, Jennifer Knight-Madden17, Rajesh Kumar25, Leslie A. Lange1, Ethan M. Lange1, Antoine Lizee21, Pissamai Maul26, Trevor Maul26, Alvaro Mayorga27, Deborah Meyers13, Dan L. Nicolae28, Timothy D. O’Connor29, Ricardo Riccio Oliveira30, Christopher O. Olopade31, Olufunmilayo Olopade28, Zhaohui S. Qin 32, Charles Rotimi 7, Nicolas Vince 21, Harold Watson33, Rainford J. Wilks17, James G. Wilson34, Steven Salzberg 35, Carole Ober36, Esteban G. Burchard22, L. Keoki Williams37, Terri H. Beaty 38, Margaret A. Taub39, Ingo Ruczinski39, CAAPA, Rasika A. Mathias4 & Kathleen C. Barnes1, Ayola Akim Adegnika40, Ganiyu Arinola41, Ulysse Ateba-Ngoa40, Gerardo Ayestas23, Hilda Bjarnadóttir42, Adolfo Correa 43, Said Omar Leiva Erazo23, Marilyn G. Foreman44, Cassandra Foster4, Li Gao4, Jingjing Gao45, Leslie Grammer11, Mark Hansen46, Tina Hartert47, Yijuan Hu32, Iain Königsberg1, Kwang-Youn A. Kim 48, Pamela Landaverde-Torres23, Javier Marrugo49, Beatriz Martinez49, Rosella Martinez23, Luis F. Mayorga23, Delmy-Aracely Mejia-Mejia50, Catherine Meza49, Solomon Musani43, Shaila Musharoff3, Oluwafemi Oluwole28, Maria Pino-Yanes 5, Hector Ramos23, Allan Saenz23, Maureen Samms-Vaughan51, Robert Schleimer11, Alan F. Scott52, Suyash S. Shringarpure3, Wei Song29, Zachary A. Szpiech 22, Raul Torres 53, Gloria Varela23, Olga Marina Vasquez54, Francisco M. De La Vega3, Lorraine B. Ware47 & Maria Yazdanbakhsh 5. 1Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. 2Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA. 3Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. 4Department of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA. 5Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA. 6Center for Human Genomics and Personalized Medicine, Wake Forest School of Medicine, Winston-Salem 27157, USA. 7Center for Research on Genomics & Global Health, National Institutes of Health, Bethesda, MD 20892, USA. 8Department of Human Genetics, Emory University, Atlanta, GA 30322, USA. 9Institute for Immunological Research, Universidad de Cartagena, Cartagena 130000, Colombia 10Immunology Service, Universidade Federal da Bahia, Salvador 401110170, Brazil. 11Department of Medicine, Northwestern University, Chicago, IL 60611, USA. 12Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 13Department of Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA. 14Universidade Federal da Bahia, Salvador 401110170, Brazil. 15Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA. 16National Human Genome Center, Howard University College of Medicine, Washington, DC 20059, USA. 17Caribbean Institute for Health Research, The University of the West Indies, Kingston 00007, Jamaica. 18Departamento de Biorregulacao, Universidade Federal da Bahia, Salvador 401110170, Brazil. 19Department of Medicine, Einstein Medical Center, Philadelphia, PA 19141, USA. 20National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. 21Université de Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie, UMR, 1064ATIP-Avenir, Equipe 5, Nantes, France. 22Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94143, USA. 23Facultad de Medicina, Universidad Católica de Honduras, San Pedro Sula 21102, Honduras. 24Universidad Tecnológica Centroamericana (UNITEC), Facultad de Ciencias Médicas, Tegucigalpa, Honduras. 25Department of Pediatrics, Northwestern University, Chicago, IL 60611, USA. 26Genetics and Epidemiology of Asthma in Barbados, The University of the West Indies, Chronic Disease Research Centre, Jemmots Lane, St. Michael BB11115, Barbados. 27Centro de Neumologia y Alergias, San Pedro Sula 21102, Honduras. 28Department of Medicine, University of Chicago, Chicago, IL 60637, USA. 29Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA. 30Laboratório de Patologia Experimental, Centro de Pesquisas Gonçalo Moniz, Salvador 40296-710, Brazil. 31Department of Medicine and Center for Global Health, University of Chicago, Chicago, IL 60637, USA. 32Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA. 33Faculty of Medical Sciences, The University of the West Indies, Queen Elizabeth Hospital, Bridgetown, St. Michael BB11000, Barbados. 34Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. 35Departments of Biomedical Engineering and Biostatistics, Johns Hopkins University, Baltimore, MD 21205, USA. 36Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. 37Center for Individualized and Genomic Medicine Research, Henry Ford Health System, Detroit, MI 48202, USA. 38Department of Epidemiology, Bloomberg School of Public Health, JHU, Baltimore, MD 21205, USA. 39Department of Biostatistics, Bloomberg School of Public Health, JHU, Baltimore, MD 21205, USA. These authors contributed equally: Rasika A. Mathias, Kathleen C. Barnes.40Centre de Recherches Médicales de Lambaréné, BP:242, Lambaréné 13901, Gabon. 41Department of Chemical Pathology, University of Ibadan, Ibadan 900001, Nigeria. 42Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland. 43Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. 44Pulmonary and Critical Care Medicine, Morehouse School of Medicine, Atlanta, GA 30310, USA. 45Data and Statistical Sciences, AbbVie, North Chicago, IL 60064, USA. 46Illumina, Inc., San Diego, CA 92122, USA. 47Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA. 48Department of Preventive Medicine, Northwestern University, Chicago, IL 60611, USA. 49Instituto de Investigaciones Immunologicas, Universidad de Cartagena, Cartagena 130000, Colombia. 50Facultad de Ciencias de la Salud, Universidad Tecnológica Centroamericana (UNITEC), San Pedro Sula 21102, Honduras. 51Department of Child Health, The University of the West Indies, Kingston 00007, Jamaica. 52Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA. 53Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA 94158, USA. 54Centro Medico de la Familia, San Pedro Sula 21102, Honduras. 55Department of Parasitology, Leiden University Medical Center, Leiden 02333, NetherlandsSubmitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-03-25T16:18:22Z No. of bitstreams: 1 Daya M Association study in African-admixed...2019.pdf: 1446713 bytes, checksum: ec386d63089da2ac2c2f15c4ef98f264 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-03-25T16:36:07Z (GMT) No. of bitstreams: 1 Daya M Association study in African-admixed...2019.pdf: 1446713 bytes, checksum: ec386d63089da2ac2c2f15c4ef98f264 (MD5)Made available in DSpace on 2019-03-25T16:36:07Z (GMT). No. of bitstreams: 1 Daya M Association study in African-admixed...2019.pdf: 1446713 bytes, checksum: ec386d63089da2ac2c2f15c4ef98f264 (MD5) Previous issue date: 2019Múltipla - ver em NotasAsthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations

Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations (vol 10, 880, 2019)

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