Using population-specific add-on polymorphisms to improve genotype imputation in underrepresented populations.
PLoS Comput Biol
; 18(1): e1009628, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-35025869
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
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Estudo de Associação Genômica Ampla
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Genética Populacional
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Genótipo
Limite:
Humans
/
Male
País/Região como assunto:
Africa
Idioma:
En
Revista:
PLoS Comput Biol
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Suíça