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 R2for 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.
authors.affiliation: Avera Institute for Human Genetics, Sioux Falls, SD, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Ehli
authors.affiliation: The Netherlands Twin Register, Vrije Universiteit (VU), Amsterdam, The Netherlands.
authors.forename: Abdel
authors.initials: A
authors.lastname: Abdellaoui
authors.affiliation: The Netherlands Twin Register, Vrije Universiteit (VU), Amsterdam, The Netherlands.
authors.forename: Iryna O
authors.initials: IO
authors.lastname: Fedko
authors.affiliation: Affymetrix Inc., Santa Clara, CA, USA.
authors.forename: Charlie
authors.initials: C
authors.lastname: Grieser
authors.affiliation: Affymetrix Inc., Santa Clara, CA, USA.
authors.forename: Sahar
authors.initials: S
authors.lastname: Nohzadeh-Malakshah
authors.affiliation: The Netherlands Twin Register, Vrije Universiteit (VU), Amsterdam, The Netherlands.
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: The Netherlands Twin Register, Vrije Universiteit (VU), Amsterdam, The Netherlands.|EMGO institute for Health and Care Research, VU and VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Eco Jc
authors.initials: EJ
authors.lastname: de Geus
authors.affiliation: Avera Institute for Human Genetics, Sioux Falls, SD, USA.|The Netherlands Twin Register, Vrije Universiteit (VU), Amsterdam, The Netherlands.|EMGO institute for Health and Care Research, VU and VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: Avera Institute for Human Genetics, Sioux Falls, SD, USA.|The Netherlands Twin Register, Vrije Universiteit (VU), Amsterdam, The Netherlands.
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Davies
authors.affiliation: The Netherlands Twin Register, Vrije Universiteit (VU), Amsterdam, The Netherlands.|EMGO institute for Health and Care Research, VU and VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jouke J
authors.initials: JJ
authors.lastname: Hottenga
mesh_terms: D055106:Genome-Wide Association Study / Q000379:methods* / Q000592:standards; D060005:Genotyping Techniques / Q000379:methods* / Q000592:standards; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity