Advancing Human Genetics Research and Drug Discovery through Exome Sequencing of the UK Biobank

• DOI: 10.1101/2020.11.02.20222232
• Publication Date: 2020-11-04T18:11:44Z
• Authors: Joseph D. Szustak...; Suganthi Balasubr...; Ariella Sasson; Shareef Khalid; Paola G. Bronson; Erika Kvikstad; Emily Wong; Daren Liu; J. Wade Davis; Carolina Haefliger; A. Katrina Loomis; Rajesh Mikkilineni; Hyun Ji Noh; Samir Wadhawan; Xiaodong Bai; Alicia Hawes; Olga Krasheninina; Ricardo Ulloa; Alex Lopez; Erin N. Smith; Jeff Waring; Christopher D. Wh...; Ellen A. Tsai; John Overton; William Salerno; Howard Jacob; Sandor Szalma; Heiko Runz; Greg Hinkle; Paul Nioi; Slavé Petrovski; Melissa R. Miller; Aris Baras; Lyndon Mitnaul; Jeffrey G. Reid
• Keywords: Exome; dbSNP; Human genetics; Indel

Abstract The UK Biobank Exome Sequencing Consortium (UKB-ESC) is a unique private/public partnership between the and eight biopharma companies that will sequence exomes of all ∼500,000 participants. Here we describe early results from exome data generated by this consortium for first ∼200,000 UKB subjects key features project enabled UKB-ESC to come together generate data. sequencing 200,643 enrollees are now accessible research community. Approximately 10M variants were observed within targeted regions, including: 8,086,176 SNPs, 370,958 indels 1,596,984 multi-allelic variants. Of ∼8M observed, 84.5% coding include 2,139,318 (25.3%) synonymous, 4,549,694 (53.8%) missense, 453,733 (5.4%) predicted loss-of-function (LOF) (initiation codon loss, premature stop codons, splicing frameshift variants) affecting at least one transcript. This open access provides rich resource rare variant genetic studies, particularly valuable drug discovery efforts utilize rare, functionally consequential Over past decade, industry has increasingly leveraged human genetics as part their development strategies. shift was motivated technical advances cost-effective scale, emergence electronic health records biobanks, maturing understanding how can increase probability successful development. Recognizing need large-scale drive discovery, value policies contribution terms Biobank, formed. precompetitive collaboration further strengthened ties academia provided teams an unprecedented opportunity interact with learn wider