The UK10K project identifies rare variants in health and disease

Article, Unknown English OPEN
Walter, Klaudia ; Min, Josine L. ; Huang, Jie ; Crooks, Lucy ; Memari, Yasin ; McCarthy, Shane ; Perry, John ; Xu, Changjiang ; Futema, Marta ; Lawson, Daniel ; Iotchkova, Valentina ; Schiffels, Stephan ; Hendricks, Audrey E. ; Danecek, Petr ; Li, Rui ; Floyd, James ; Wain, Louise ; Barroso, Inês ; Humphries, Steve ; Hurles, Matthew ; Zeggini, Eleftheria ; Barrett, Jeffrey ; Plagnol, Vincent ; Richards, Brent ; Greenwood, Celia ; Timpson, Nicholas ; Durbin, Richard ; Bala, Senduran ; Clapham, Peter ; Coates, Guy ... view all 242 authors (2015)
  • Publisher: Nature Publishing Group
  • Journal: (issn: 0028-0836, vol: 526, pp: 82-90)
  • Related identifiers: doi: 10.17863/CAM.24790, doi: 10.1038/nature14962, pmc: PMC4773891
  • Subject: Receptors, LDL | Adiponectin | /dk/atira/pure/researchoutput/pubmedpublicationtype/D013485 | Lipid Metabolism | UK10K Consortium | Multidisciplinary Sciences | SEQUENCE VARIATION | Research Support, Non-U.S. Gov't | HERITABILITY | Molecular Sequence Annotation | COMMON | Sequence Analysis, DNA | Science & Technology, Multidisciplinary Sciences, Science & Technology, Genome-Wide Association, Of-Function Mutations, Low-Frequency, Incidental Findings, Sequence Variation, Complex Traits, Population, Common, Heritability, APOC3 | Genomics | INCIDENTAL FINDINGS | Science & Technology - Other Topics | APOC3 | Female | Alleles | Genome, Human | MD Multidisciplinary | Disease | OF-FUNCTION MUTATIONS | /dk/atira/pure/researchoutput/pubmedpublicationtype/D016428 | United Kingdom | Health | Genetic Variation | COMPLEX TRAITS | Great Britain | Triglycerides | Reference Standards | Article | POPULATION | Genetics, Medical | genetics,UK10K,Whole-genome sequencing | Exome | Science & Technology | Genome-Wide Association Study | Cohort Studies | Genetics, Population | General Science & Technology | Journal Article | Genetic Predisposition to Disease | GENOME-WIDE ASSOCIATION | LOW-FREQUENCY | Humans | Male

<p>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 (<i>APOB</i>), adiponectin (<i>ADIPOQ</i>) and low-density lipoprotein cholesterol (<i>LDLR</i> and <i>RGAG1</i>) 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.</p>