Uk bileve axiom

The samples from the UK Biobank were genotyped using two different Affymetrix chips – the UK BiLEVE Axiom in the first 50,000 individuals^{67 (link)}, and the Affymetrix UK Biobank Axiom array^{68 (link)} in the remaining participants. In total, 428,864 participants have been genotyped and 131,272 WGS. Samples with variant yield below 98% were filtered out and any duplicate samples were removed. High-quality sequence variants and indels to a mean depth of at least 20× were identified using Graphtyper^{60 (link),61 (link)}. Quality-controlled chip-genotype data were phased using Shapeit4^{69 (link)} and variants where at least 50% of the samples had a genotype quality score above 0 were used to prepare a haplotype reference panel using in-house tools and the long-range phased chip data. The variants in the haplotype reference panel were imputed into the chip-genotyped samples using the same in-house tools and methods described for the Icelandic data^{47 (link),62 (link)}.

The GWASs in Iceland were performed with 32.5 million markers identified through whole-genome sequencing of 15,520 Icelanders to an average genome-wide coverage of 34X and subsequently imputed into 151,677 chip-typed individuals, as well as their first and second degree relatives. The imputation has been extensively described in recent publications^{54 (link)}. Genotyping of UK biobank samples was performed using a custom-made Affymetrix chip, UK BiLEVE Axiom^{55 (link)}, and with the Affymetrix UK Biobank Axiom array^{56 (link)}. Imputation was performed by the Wellcome Trust Centre for Human Genetics, using the Haplotype Reference Consortium (HRC) and the UK10K haplotype resources. This yields a total of 96 million imputed variants, however only 27 million variants imputed using the HRC reference set passed the quality filters used in our study.

The GWAS summary data for DVT were obtained from the UK Biobank (UK Biobank fields: 20002). In short, the UK Biobank participants were of European ancestry. The UK Biobank contains the ancestry genetic association maps for 118 non-binary traits and 660 binary traits for a total of 452,264 participants (males and females). In total, 9,059 DVT cases and 443,205 controls were included in our study. The Affymetrix UK BiLEVE Axiom and Affymetrix UK Biobank Axiom arrays were used for genotyping. We excluded individuals who were identified by the UK Biobank as outliers based on either the genotyping missingness rate or heterogeneity, whose sex inferred from the genotypes did not match their self-reported sex, and who were not of European ancestry. Finally, we removed individuals with missingness >5% across variants that passed our quality control procedure and those that had a missing phenotype for 40 or more traits. An estimated 90 million genetic variants were identified in the Haplotype Reference Consortium, 1000 Genomes, and UK10K projects. After quality control, 62,394 genotype variants and 9,113,133 variable estimates were obtained. In previous studies, all participants signed an informed consent form and obtained approval from the ethics committee. Detailed information on genotyping, estimation and quality control can be found in a previous study (30 (link)).