title: The UK10K project identifies rare variants in health and disease.
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.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Walter
authors.forename: Josine L
authors.initials: JL
authors.lastname: Min
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Lucy
authors.initials: L
authors.lastname: Crooks
authors.forename: Yasin
authors.initials: Y
authors.lastname: Memari
authors.forename: Shane
authors.initials: S
authors.lastname: McCarthy
authors.forename: John R B
authors.initials: JR
authors.lastname: Perry
authors.forename: ChangJiang
authors.initials: C
authors.lastname: Xu
authors.forename: Marta
authors.initials: M
authors.lastname: Futema
authors.forename: Daniel
authors.initials: D
authors.lastname: Lawson
authors.forename: Valentina
authors.initials: V
authors.lastname: Iotchkova
authors.forename: Stephan
authors.initials: S
authors.lastname: Schiffels
authors.forename: Audrey E
authors.initials: AE
authors.lastname: Hendricks
authors.forename: Petr
authors.initials: P
authors.lastname: Danecek
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: James
authors.initials: J
authors.lastname: Floyd
authors.forename: Louise V
authors.initials: LV
authors.lastname: Wain
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Barrett
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
authors.forename: Celia M T
authors.initials: CM
authors.lastname: Greenwood
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: Richard
authors.initials: R
authors.lastname: Durbin
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
mesh_terms: D052242:Adiponectin / Q000097:blood; D000483:Alleles; D015331:Cohort Studies; D004194:Disease / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005826:Genetics, Medical; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D023281:Genomics; D006262:Health; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D058977:Molecular Sequence Annotation; D011973:Receptors, LDL / Q000235:genetics; D012015:Reference Standards; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood; D006113:United Kingdom
chemical_list: D052242:Adiponectin; D011973:Receptors, LDL; D014280:Triglycerides