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

Andrés Jiménez-Kaufmann, Amanda Y. Chong, Adrián Cortés, Consuelo D. Quinto-Cortés, Selene L. Fernandez-Valverde, Leticia Ferreyra-Reyes, Luis Pablo Cruz-Hervert, Santiago G. Medina-Muñoz, Mashaal Sohail, María J. Palma-Martinez, Gudalupe Delgado-Sánchez, Norma Mongua-Rodríguez, Alexander J. Mentzer, Adrian V.S. Hill, Hortensia Moreno-Macías, Alicia Huerta-Chagoya, Carlos A. Aguilar-Salinas, Michael Torres, Hie Lim Kim, Namrata KalsiStephan C. Schuster, Teresa Tusié-Luna, Diego Ortega Del-Vecchyo, Lourdes García-García*, Andrés Moreno-Estrada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number719791
JournalFrontiers in Genetics
Volume12
DOIs
Publication statusPublished - Jan 3 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
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.

ASJC Scopus Subject Areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Keywords

  • GWAS
  • Imputation
  • Latin Americans
  • Native American ancestry
  • reference panels
  • underrepresented populations

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