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Brent, Soranzo, Nicole ORCID: 0000-0003-1095-3852, Spector, Timothy D., Stalker, Jim, Timpson, Nicholas J., Zeggini, Eleftheria ORCID: 0000-0003-4238-659X, Amuzu, Antoinette, Casas, Juan Pablo, Chambers, John C., Cocca, Massimiliano ORCID: 0000-0002-1127-7596, Dedoussis, George, Gambaro, Giovanni, Gasparini, Paolo ORCID: 0000-0002-0859-0856, Gaunt, Tom R., Huang, Jie ORCID: 0000-0002-9036-4304, Iotchkova, Valentina ORCID: 0000-0001-5057-0210, Isaacs, Aaron, Johnson, Jon ORCID: 0000-0001-8482-1620, Kleber, Marcus E., Kooner, Jaspal S., Langenberg, Claudia, Luan, Jian'an, Malerba, Giovanni ORCID: 0000-0001-8705-8560, Maerz, Winfried, Matchan, Angela, Min, Josine L., Morris, Richard ORCID: 0000-0001-7240-4563, Nordestgaard, Borge G., Benn, Marianne ORCID: 0000-0002-1701-595X, Ring, Susan, Scott, Robert A., Soranzo, Nicole ORCID: 0000-0003-1095-3852, Southam, Lorraine, Timpson, Nicholas J., Toniolo, Daniela ORCID: 0000-0001-9545-6032, Traglia, Michela, Tybjaerg-Hansen, Anne, van Duijn, Cornelia M., van Leeuwen, Elisabeth M., Varbo, Anette, Whincup, Peter ORCID: 0000-0002-5589-4107, Zaza, Gianluigi ORCID: 0000-0002-6004-6196, Zeggini, Eleftheria ORCID: 0000-0003-4238-659X and Zhang, Weihua (2015). The UK10K project identifies rare variants in health and disease. Nature, 526 (7571). S. 82 - 103. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

Full text not available from this repository.

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, 7x) or exomes (high read depth, 80x) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
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Min, Josine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Crooks, LucyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Memari, YasinUNSPECIFIEDorcid.org/0000-0002-1747-542XUNSPECIFIED
McCarthy, ShaneUNSPECIFIEDorcid.org/0000-0002-2715-4187UNSPECIFIED
Perry, John R. B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xu, ChangJiangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Futema, MartaUNSPECIFIEDorcid.org/0000-0002-2120-2088UNSPECIFIED
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Wain, Louise V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Humphries, Steve E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Barrett, Jeffrey C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plagnol, VincentUNSPECIFIEDorcid.org/0000-0002-5597-9215UNSPECIFIED
Richards, J. BrentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greenwood, Celia M. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Cox, TonyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, AllanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Danecek, PetrUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Du, YuanpingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durbin, RichardUNSPECIFIEDorcid.org/0000-0002-9130-1006UNSPECIFIED
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Joyce, ChrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keane, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolb-Kokocinski, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langford, CordeliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, YingruiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Lin, HongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Cocca, MassimilianoUNSPECIFIEDorcid.org/0000-0002-1127-7596UNSPECIFIED
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Carss, KerenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chatterjee, KrishnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cirak, SebahattinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cosgrove, CatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durbin, RichardUNSPECIFIEDorcid.org/0000-0002-9130-1006UNSPECIFIED
Fitzpatrick, David R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Floyd, JamesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foley, A. ReghanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franklin, Christopher S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Futema, MartaUNSPECIFIEDorcid.org/0000-0002-2120-2088UNSPECIFIED
Grozeva, DetelinaUNSPECIFIEDorcid.org/0000-0003-3239-8415UNSPECIFIED
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McCarthy, ShaneUNSPECIFIEDorcid.org/0000-0002-2715-4187UNSPECIFIED
Mitchison, Hannah M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muddyman, DawnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muntoni, FrancescoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
O'Rahilly, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Onoufriadis, AlexandrosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parker, VictoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Payne, FelicityUNSPECIFIEDorcid.org/0000-0003-4228-581XUNSPECIFIED
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Raymond, F. LucyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roberts, NicolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Savage, David B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scambler, PeterUNSPECIFIEDorcid.org/0000-0002-1487-4628UNSPECIFIED
Schmidts, MiriamUNSPECIFIEDorcid.org/0000-0002-1714-6749UNSPECIFIED
Schoenmakers, NadiaUNSPECIFIEDorcid.org/0000-0002-0847-2884UNSPECIFIED
Semple, Robert K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Serra, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spasic-Boskovic, OliveraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stevens, ElizabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Kogelenberg, MargrietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vijayarangakannan, ParthibanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walter, KlaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Williamson, Kathleen A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilson, CrispianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whyte, TamiekaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ciampi, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greenwood, Celia M. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hendricks, Audrey E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, RuiUNSPECIFIEDorcid.org/0000-0001-8353-6772UNSPECIFIED
Metrustry, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oualkacha, KarimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tachmazidou, IoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xu, ChangJiangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeggini, EleftheriaUNSPECIFIEDorcid.org/0000-0003-4238-659XUNSPECIFIED
Bobrow, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolton, Patrick F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durbin, RichardUNSPECIFIEDorcid.org/0000-0002-9130-1006UNSPECIFIED
Fitzpatrick, David R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Griffin, HeatherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hurles, Matthew E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Kennedy, KarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kent, AlastairUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muddyman, DawnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muntoni, FrancescoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raymond, F. LucyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Semple, Robert K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smee, CarolUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spector, Timothy D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timpson, Nicholas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Charlton, RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ekong, RosemaryUNSPECIFIEDorcid.org/0000-0002-5984-7893UNSPECIFIED
Futema, MartaUNSPECIFIEDorcid.org/0000-0002-2120-2088UNSPECIFIED
Humphries, Steve E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khawaja, FarrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopes, Luis R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Migone, NicolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Payne, Stewart J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plagnol, VincentUNSPECIFIEDorcid.org/0000-0002-5597-9215UNSPECIFIED
Pollitt, Rebecca C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Povey, SueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ridout, Cheryl K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robinson, Rachel L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scott, Richard H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shaw, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Syrris, PetrosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor, RohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vandersteen, Anthony M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barrett, Jeffrey C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barroso, InesUNSPECIFIEDorcid.org/0000-0001-5800-4520UNSPECIFIED
Smith, George DaveyUNSPECIFIEDorcid.org/0000-0002-1407-8314UNSPECIFIED
Durbin, RichardUNSPECIFIEDorcid.org/0000-0002-9130-1006UNSPECIFIED
Farooqi, I. SadafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fitzpatrick, David R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Kaye, JaneUNSPECIFIEDorcid.org/0000-0002-7311-4725UNSPECIFIED
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Muddyman, DawnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, Michael J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palotie, AarnoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richards, J. BrentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soranzo, NicoleUNSPECIFIEDorcid.org/0000-0003-1095-3852UNSPECIFIED
Spector, Timothy D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stalker, JimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timpson, Nicholas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeggini, EleftheriaUNSPECIFIEDorcid.org/0000-0003-4238-659XUNSPECIFIED
Amuzu, AntoinetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Casas, Juan PabloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chambers, John C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cocca, MassimilianoUNSPECIFIEDorcid.org/0000-0002-1127-7596UNSPECIFIED
Dedoussis, GeorgeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gambaro, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gasparini, PaoloUNSPECIFIEDorcid.org/0000-0002-0859-0856UNSPECIFIED
Gaunt, Tom R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, JieUNSPECIFIEDorcid.org/0000-0002-9036-4304UNSPECIFIED
Iotchkova, ValentinaUNSPECIFIEDorcid.org/0000-0001-5057-0210UNSPECIFIED
Isaacs, AaronUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, JonUNSPECIFIEDorcid.org/0000-0001-8482-1620UNSPECIFIED
Kleber, Marcus E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kooner, Jaspal S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langenberg, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luan, Jian'anUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malerba, GiovanniUNSPECIFIEDorcid.org/0000-0001-8705-8560UNSPECIFIED
Maerz, WinfriedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matchan, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Min, Josine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morris, RichardUNSPECIFIEDorcid.org/0000-0001-7240-4563UNSPECIFIED
Nordestgaard, Borge G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benn, MarianneUNSPECIFIEDorcid.org/0000-0002-1701-595XUNSPECIFIED
Ring, SusanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scott, Robert A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soranzo, NicoleUNSPECIFIEDorcid.org/0000-0003-1095-3852UNSPECIFIED
Southam, LorraineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timpson, Nicholas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toniolo, DanielaUNSPECIFIEDorcid.org/0000-0001-9545-6032UNSPECIFIED
Traglia, MichelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tybjaerg-Hansen, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Duijn, Cornelia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Leeuwen, Elisabeth M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Varbo, AnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whincup, PeterUNSPECIFIEDorcid.org/0000-0002-5589-4107UNSPECIFIED
Zaza, GianluigiUNSPECIFIEDorcid.org/0000-0002-6004-6196UNSPECIFIED
Zeggini, EleftheriaUNSPECIFIEDorcid.org/0000-0003-4238-659XUNSPECIFIED
Zhang, WeihuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-392210
DOI: 10.1038/nature14962
Journal or Publication Title: Nature
Volume: 526
Number: 7571
Page Range: S. 82 - 103
Date: 2015
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; LOW-FREQUENCY; INCIDENTAL FINDINGS; COMMON; HERITABILITY; EXOME; APOC3; RISK; LOCI; SNPMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39221

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