The UK10K Project Identifies Rare Variants in Health and Disease

Nature. 2015 Oct 1;526(7571):82-90. doi: 10.1038/nature14962. Epub 2015 Sep 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Alleles
  • Cohort Studies
  • Disease / genetics*
  • Exome / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation / genetics*
  • Genetics, Medical
  • Genetics, Population
  • Genome, Human / genetics*
  • Genome-Wide Association Study
  • Genomics
  • Health*
  • Humans
  • Lipid Metabolism / genetics
  • Male
  • Molecular Sequence Annotation
  • Receptors, LDL / genetics
  • Reference Standards
  • Sequence Analysis, DNA
  • Triglycerides / blood
  • United Kingdom

Substances

  • Adiponectin
  • Receptors, LDL
  • Triglycerides

Grant support