Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784633723439808512 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8762266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT jimenezkaufmannandres imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT chongamanday imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT cortesadrian imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT quintocortesconsuelod imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT fernandezvalverdeselenel imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT ferreyrareyesleticia imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT cruzhervertluispablo imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT medinamunozsantiagog imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT sohailmashaal imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT palmamartinezmariaj imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT delgadosanchezgudalupe imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT monguarodrigueznorma imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT mentzeralexanderj imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT hilladrianvs imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT morenomaciashortensia imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT huertachagoyaalicia imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT aguilarsalinascarlosa imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT torresmichael imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT kimhielim imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT kalsinamrata imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT schusterstephanc imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT tusielunateresa imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT delvecchyodiegoortega imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT garciagarcialourdes imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes AT morenoestradaandres imputationperformanceinlatinamericanpopulationsimprovingrarevariantsrepresentationwiththeinclusionofnativeamericangenomes |