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.

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Persistent URL dx.doi.org/10.1038/nature14962, hdl.handle.net/1765/81634
Journal Nature: international weekly journal of science
Citation
Walter, K, Min, J.L, Huang, J, Crooks, L, Memari, Y, McCarthy, S, … Zhang, W. (2015). The UK10K project identifies rare variants in health and disease. Nature: international weekly journal of science, 526(7571), 82–89. doi:10.1038/nature14962