Low-pass sequencing increases the power of GWAS and decreases measurement error of polygenic risk scores compared to genotyping arrays.
Genome Res
; 31(4): 529-537, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33536225
ABSTRACT
Low-pass sequencing (sequencing a genome to an average depth less than 1× coverage) combined with genotype imputation has been proposed as an alternative to genotyping arrays for trait mapping and calculation of polygenic scores. To empirically assess the relative performance of these technologies for different applications, we performed low-pass sequencing (targeting coverage levels of 0.5× and 1×) and array genotyping (using the Illumina Global Screening Array [GSA]) on 120 DNA samples derived from African- and European-ancestry individuals that are part of the 1000 Genomes Project. We then imputed both the sequencing data and the genotyping array data to the 1000 Genomes Phase 3 haplotype reference panel using a leave-one-out design. We evaluated overall imputation accuracy from these different assays as well as overall power for GWAS from imputed data and computed polygenic risk scores for coronary artery disease and breast cancer using previously derived weights. We conclude that low-pass sequencing plus imputation, in addition to providing a substantial increase in statistical power for genome-wide association studies, provides increased accuracy for polygenic risk prediction at effective coverages of â¼0.5× and higher compared to the Illumina GSA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estudo de Associação Genômica Ampla
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Sequenciamento de Nucleotídeos em Larga Escala
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Genótipo
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article