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Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American geno...

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Autores principales: Jiménez-Kaufmann, Andrés, Chong, Amanda Y., Cortés, Adrián, Quinto-Cortés, Consuelo D., Fernandez-Valverde, Selene L., Ferreyra-Reyes, Leticia, Cruz-Hervert, Luis Pablo, Medina-Muñoz, Santiago G., Sohail, Mashaal, Palma-Martinez, María J., Delgado-Sánchez, Gudalupe, Mongua-Rodríguez, Norma, Mentzer, Alexander J., Hill, Adrian V. S., Moreno-Macías, Hortensia, Huerta-Chagoya, Alicia, Aguilar-Salinas, Carlos A., Torres, Michael, Kim, Hie Lim, Kalsi, Namrata, Schuster, Stephan C., Tusié-Luna, Teresa, Del-Vecchyo, Diego Ortega, García-García, Lourdes, Moreno-Estrada, Andrés
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762266/
https://www.ncbi.nlm.nih.gov/pubmed/35046991
http://dx.doi.org/10.3389/fgene.2021.719791
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author Jiménez-Kaufmann, Andrés
Chong, Amanda Y.
Cortés, Adrián
Quinto-Cortés, Consuelo D.
Fernandez-Valverde, Selene L.
Ferreyra-Reyes, Leticia
Cruz-Hervert, Luis Pablo
Medina-Muñoz, Santiago G.
Sohail, Mashaal
Palma-Martinez, María J.
Delgado-Sánchez, Gudalupe
Mongua-Rodríguez, Norma
Mentzer, Alexander J.
Hill, Adrian V. S.
Moreno-Macías, Hortensia
Huerta-Chagoya, Alicia
Aguilar-Salinas, Carlos A.
Torres, Michael
Kim, Hie Lim
Kalsi, Namrata
Schuster, Stephan C.
Tusié-Luna, Teresa
Del-Vecchyo, Diego Ortega
García-García, Lourdes
Moreno-Estrada, Andrés
author_facet Jiménez-Kaufmann, Andrés
Chong, Amanda Y.
Cortés, Adrián
Quinto-Cortés, Consuelo D.
Fernandez-Valverde, Selene L.
Ferreyra-Reyes, Leticia
Cruz-Hervert, Luis Pablo
Medina-Muñoz, Santiago G.
Sohail, Mashaal
Palma-Martinez, María J.
Delgado-Sánchez, Gudalupe
Mongua-Rodríguez, Norma
Mentzer, Alexander J.
Hill, Adrian V. S.
Moreno-Macías, Hortensia
Huerta-Chagoya, Alicia
Aguilar-Salinas, Carlos A.
Torres, Michael
Kim, Hie Lim
Kalsi, Namrata
Schuster, Stephan C.
Tusié-Luna, Teresa
Del-Vecchyo, Diego Ortega
García-García, Lourdes
Moreno-Estrada, Andrés
author_sort Jiménez-Kaufmann, Andrés
collection PubMed
description Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.
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spelling pubmed-87622662022-01-18 Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes Jiménez-Kaufmann, Andrés Chong, Amanda Y. Cortés, Adrián Quinto-Cortés, Consuelo D. Fernandez-Valverde, Selene L. Ferreyra-Reyes, Leticia Cruz-Hervert, Luis Pablo Medina-Muñoz, Santiago G. Sohail, Mashaal Palma-Martinez, María J. Delgado-Sánchez, Gudalupe Mongua-Rodríguez, Norma Mentzer, Alexander J. Hill, Adrian V. S. Moreno-Macías, Hortensia Huerta-Chagoya, Alicia Aguilar-Salinas, Carlos A. Torres, Michael Kim, Hie Lim Kalsi, Namrata Schuster, Stephan C. Tusié-Luna, Teresa Del-Vecchyo, Diego Ortega García-García, Lourdes Moreno-Estrada, Andrés Front Genet Genetics Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research. Frontiers Media S.A. 2022-01-03 /pmc/articles/PMC8762266/ /pubmed/35046991 http://dx.doi.org/10.3389/fgene.2021.719791 Text en Copyright © 2022 Jiménez-Kaufmann, Chong, Cortés, Quinto-Cortés, Fernandez-Valverde, Ferreyra-Reyes, Cruz-Hervert, Medina-Muñoz, Sohail, Palma-Martinez, Delgado-Sánchez, Mongua-Rodríguez, Mentzer, Hill, Moreno-Macías, Huerta-Chagoya, Aguilar-Salinas, Torres, Kim, Kalsi, Schuster, Tusié-Luna, Del-Vecchyo, García-García and Moreno-Estrada. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Jiménez-Kaufmann, Andrés
Chong, Amanda Y.
Cortés, Adrián
Quinto-Cortés, Consuelo D.
Fernandez-Valverde, Selene L.
Ferreyra-Reyes, Leticia
Cruz-Hervert, Luis Pablo
Medina-Muñoz, Santiago G.
Sohail, Mashaal
Palma-Martinez, María J.
Delgado-Sánchez, Gudalupe
Mongua-Rodríguez, Norma
Mentzer, Alexander J.
Hill, Adrian V. S.
Moreno-Macías, Hortensia
Huerta-Chagoya, Alicia
Aguilar-Salinas, Carlos A.
Torres, Michael
Kim, Hie Lim
Kalsi, Namrata
Schuster, Stephan C.
Tusié-Luna, Teresa
Del-Vecchyo, Diego Ortega
García-García, Lourdes
Moreno-Estrada, Andrés
Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes
title Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes
title_full Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes
title_fullStr Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes
title_full_unstemmed Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes
title_short Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes
title_sort imputation performance in latin american populations: improving rare variants representation with the inclusion of native american genomes
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762266/
https://www.ncbi.nlm.nih.gov/pubmed/35046991
http://dx.doi.org/10.3389/fgene.2021.719791
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