A method to customize population-specific arrays for genome-wide association testing.
Eur J Hum Genet
; 25(2): 267-270, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-27876820
ABSTRACT
As an example of optimizing population-specific genotyping assays using a whole-genome sequence reference set, we detail the approach that followed to design the Axiom-NL array which is characterized by an improved imputation backbone based on the Genome of the Netherlands (GoNL) reference sequence and, compared with earlier arrays, a more comprehensive inclusion of SNPs on chromosomes X, Y, and the mitochondria. Common variants on the array were selected to be compatible with the Illumina Psych Array and the Affymetrix UK Biobank Axiom array. About 3.5% of the array (23 977 markers) represents SNPs from the GWAS catalog, including SNPs at FTO, APOE, Ion-channels, killer-cell immunoglobulin-like receptors, and HLA. Around 26 000 markers associated with common psychiatric disorders are included, as well as 6705 markers suggested to be associated with fertility and twinning. The platform can thus be used for risk profiling, detection of new variants, as well as ancestry determination. Results of coverage tests in 249 unrelated subjects with GoNL-based sequence data show that after imputation with 1000G as a reference, the median concordance between original and imputed genotypes is above 98%. The median imputation quality R2 for MAF thresholds of 0.001, 0.01, 0.05, and >0.05 are 0.05, 0.28, 0.80, 0.99, respectively, for the 1000G imputed SNPs, with a similar quality for the autosomes and X chromosome, showing a good genome-wide coverage for association studies after imputation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Análise de Sequência com Séries de Oligonucleotídeos
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Estudo de Associação Genômica Ampla
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Técnicas de Genotipagem
Tipo de estudo:
Diagnostic_studies
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Evaluation_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Eur J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos