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Using population-specific add-on polymorphisms to improve genotype imputation in underrepresented populations

Xu, Z. M. and Rüeger, S. and Zwyer, M. and Brites, D. and Hiza, H. and Reinhard, M. and Rutaihwa, L. and Borrell, S. and Isihaka, F. and Temba, H. and Maroa, T. and Naftari, R. and Hella, J. and Sasamalo, M. and Reither, K. and Portevin, D. and Gagneux, S. and Fellay, J.. (2022) Using population-specific add-on polymorphisms to improve genotype imputation in underrepresented populations. PLoS Comput Biol, 18 (1). e1009628.

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Official URL: https://edoc.unibas.ch/91016/

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Abstract

Genome-wide association studies rely on the statistical inference of untyped variants, called imputation, to increase the coverage of genotyping arrays. However, the results are often suboptimal in populations underrepresented in existing reference panels and array designs, since the selected single nucleotide polymorphisms (SNPs) may fail to capture population-specific haplotype structures, hence the full extent of common genetic variation. Here, we propose to sequence the full genomes of a small subset of an underrepresented study cohort to inform the selection of population-specific add-on tag SNPs and to generate an internal population-specific imputation reference panel, such that the remaining array-genotyped cohort could be more accurately imputed. Using a Tanzania-based cohort as a proof-of-concept, we demonstrate the validity of our approach by showing improvements in imputation accuracy after the addition of our designed add-on tags to the base H3Africa array.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Ecology and Evolution Unit (Gagneux)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medicine (MED) > Clinical Research (Reither)
UniBasel Contributors:Zwyer, Michaela and Brites, Daniela and Hiza, Hellen and Reinhard, Miriam and Rutaihwa, Liliana and Borrell Farnov, Sonia and Reither, Klaus and Portevin, Damien and Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1553-7358 (Electronic)1553-734X (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:28 Dec 2022 09:55
Deposited On:28 Dec 2022 09:55

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