A method to customize population-specific arrays for genome-wide association testing

E.A. Ehli, A. Abdellaoui, I.O. Fedko, C. Grieser, S. Nohzadeh-Malakshah, G. Willemsen, E.J.C. de Geus, D.I. Boomsma, G.E. Davies, J.J. Hottenga

Research output: Contribution to JournalArticleAcademicpeer-review

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 R
LanguageEnglish
Pages267-270
JournalEuropean Journal of Human Genetics
Volume25
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

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Single Nucleotide Polymorphism
Genome
Netherlands
KIR Receptors
Population
Y Chromosome
Genome-Wide Association Study
X Chromosome
Ion Channels
Fertility
Psychiatry
Mitochondria
Genotype

Cite this

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title = "A method to customize population-specific arrays for genome-wide association testing",
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 R",
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A method to customize population-specific arrays for genome-wide association testing. / Ehli, E.A.; Abdellaoui, A.; Fedko, I.O.; Grieser, C.; Nohzadeh-Malakshah, S.; Willemsen, G.; de Geus, E.J.C.; Boomsma, D.I.; Davies, G.E.; Hottenga, J.J.

In: European Journal of Human Genetics, Vol. 25, No. 2, 01.02.2017, p. 267-270.

Research output: Contribution to JournalArticleAcademicpeer-review

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