Stephen, Damjan & Allan co-author UK Biobank paper

Genome-Wide Genetic Data on ~500,000 UK Biobank Participants

Genome-wide genetic data on ~500,000 UK Biobank participants
Clare Bycroft, Colin Freeman, Desislava Petkova, Gavin Band,  Lloyd T Elliott,  Kevin Sharp,  Allan Motyer,  Damjan Vukcevic, Olivier Delaneau, Jared O'Connell, Adrian Cortes, Samantha Welsh, Gil McVean,  Stephen Leslie, Peter Donnelly, Jonathan Marchini. doi:

Stephen Leslie, Damjan Vukcevic and Allan Motyer contributed to the UK Biobank Genetics paper, recently published in bioRxiv.

They describe the genome-wide genotype data (~805,000 markers) collected on all individuals in the cohort and its quality control procedures. Genotype data on this scale offers novel opportunities for assessing quality issues, although the wide range of ancestries of the individuals in the cohort also creates particular challenges. They also conducted a set of analyses that reveal properties of the genetic data (such as population structure and relatedness) that can be important for downstream analyses.

In addition, they phased and imputed genotypes into the dataset, using computationally efficient methods combined with the Haplotype Reference Consortium (HRC) and UK10K haplotype resource. This increases the number of testable variants by over 100-fold to ~96 million variants. They also imputed classical allelic variation at 11 human leukocyte antigen (HLA) genes, and as a quality control check of this imputation, they replicate signals of known associations between HLA alleles and many common diseases.

They describe tools that allow efficient genome-wide association studies (GWAS) of multiple traits and fast phenome-wide association studies (PheWAS), which work together with a new compressed file format that has been used to distribute the dataset. As a further check of the genotyped and imputed datasets, they performed a test-case genome-wide association scan on a well-studied human trait, standing height.

Figure 1: Summary of UK Biobank genotyping array content. This is a schematic representation of the different categories of content on the UK Biobank Axiom array. Numbers indicate the approximate count of markers within each category, ignoring any overlap.