The UK10K project identifies rare variants in health and disease

By Klaudia Walter, J. Min, Jie Huang, L. Crooks, Y. Memari, Shane A. McCarthy, J. Perry, Changjiang Xu, M. Futema, Daniel J. Lawson and 231 more. Nature, 2015

1,063 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b167deb51b0a8307d6b807c48546a2df4f94483e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease (2016, background): “[10]Gastrointestinal Unit, Wester General Hospital University of Edinburgh, Edinburgh, UK”
A generalized linear mixed model association tool for biobank-scale data (2021, methodology): “SNP imputation was conducted by the UKB analysis team using whole-genome sequence data from the Haplotype Reference Consortium 45 and the UK10K project 46 as the reference panels.”
dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Non-synonymous and Splice Site SNVs (2016, background): “…[Shihab et al., 2015], and DANN [Quang et al., 2015]; two conservation scores: 2× phastCons [Siepel et al., 2005], and allele frequencies from the UK10K cohorts [UK10K Consortium et al., 2015]; and the Exome Aggregation Consortium [Exome Aggregation Consortium et al., 2015] (ExAC), among others.”