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

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...

Full description

Saved in:
Bibliographic Details
Published in:PLoS computational biology 2022-01, Vol.18 (1), p.e1009628-e1009628
Main Authors: Xu, Zhi Ming, Rüeger, Sina, Zwyer, Michaela, Brites, Daniela, Hiza, Hellen, Reinhard, Miriam, Rutaihwa, Liliana, Borrell, Sonia, Isihaka, Faima, Temba, Hosiana, Maroa, Thomas, Naftari, Rastard, Hella, Jerry, Sasamalo, Mohamed, Reither, Klaus, Portevin, Damien, Gagneux, Sebastien, Fellay, Jacques
Format: Article
Language:English
Subjects:
Accuracy
Arrays
Biobanks
Biology and Life Sciences
Computational Biology - methods
Consortia
Design
Genealogy
Genetic diversity
Genetic polymorphisms
Genetics, Population - methods
Genetics, Population - standards
Genome-wide association studies
Genome-Wide Association Study - methods
Genome-Wide Association Study - standards
Genomes
Genotype
Genotype & phenotype
Genotyping
Haplotypes
Humans
Male
Nucleotides
Observations
Polymorphism, Single Nucleotide - genetics
Population studies
Populations
Research and Analysis Methods
Single-nucleotide polymorphism
Statistical inference
Tanzania
Tuberculosis
Y chromosomes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1009628