UK10K Consortium; Walter, Klaudia; Min, Josine L; Huang, Jie; Crooks, Lucy; Memari, Yasin; McCarthy, Shane; Perry, John RB; Xu, ChangJiang; Futema, Marta; +19 more... Lawson, Daniel; Iotchkova, Valentina; Schiffels, Stephan; Hendricks, Audrey E; Danecek, Petr; Li, Rui; Floyd, James; Wain, Louise V; Barroso, Inês; Humphries, Steve E; Hurles, Matthew E; Zeggini, Eleftheria; Barrett, Jeffrey C; Plagnol, Vincent; Richards, J Brent; Greenwood, Celia MT; Timpson, Nicholas J; Durbin, Richard; Soranzo, Nicole; (2015) The UK10K project identifies rare variants in health and disease. Nature, 526 (7571). pp. 82-90. ISSN 0028-0836 DOI: https://doi.org/10.1038/nature14962
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Abstract
The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.