Stephan Schiffels

Population Genetics – Computational Methods - Human History

et al. 2015

The UK10K project identifies rare variants in health and disease. Nature. Published October 1, 2015.

Authors: UK10K Consortium , Klaudia Walter, Josine L Min, Jie Huang, Lucy Crooks, Yasin Memari, Shane McCarthy, John R B Perry, Changjiang Xu, Marta Futema, Daniel Lawson, Valentina Iotchkova, Stephan Schiffels, Audrey E Hendricks, Petr Danecek, Rui Li, James Floyd, Louise V Wain, Inês Barroso, Steve E Humphries, Matthew E Hurles, Eleftheria Zeggini, Jeffrey C Barrett, Vincent Plagnol, J Brent Richards, Celia M T Greenwood, Nicholas J Timpson, Richard Durbin and Nicole Soranzo

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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.