Analysis with the exome array identifies multiple new independent variants in lipid loci

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Kanoni, StavroulaQueen Mary University (author)

Analysis with the exome array identifies multiple new independent variants in lipid loci

Article/chapterEnglish2016

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2016-07-27
Oxford University Press (OUP),2016
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LIBRIS-ID:oai:DiVA.org:umu-129174
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-129174URI
https://doi.org/10.1093/hmg/ddw227DOI
https://lup.lub.lu.se/record/442dca1f-de73-40cd-a9ac-2c9d40e3dcfdURI
http://kipublications.ki.se/Default.aspx?queryparsed=id:135322646URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.

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Masca, Nicholas G DUniversity of Leicester,National and Kapodistrian University of Athens (author)
Stirrups, Kathleen EQueen Mary University (author)
Varga, Tibor V.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Massachusetts General Hospital,Broad Institute(Swepub:lu)med-tv_ (author)
Warren, Helen RQueen Mary University (author)
Scott, Robert AAddenbrooke's Hospital (author)
Southam, LorraineWellcome Trust Sanger Institute (author)
Zhang, WeihuaImperial College London (author)
Yaghootkar, HaniehUniversity of Exeter (author)
Müller-Nurasyid, MartinaHelmholtz Zentrum München (author)
Couto Alves, AlexessanderImperial College London (author)
Strawbridge, Rona JKarolinska Institutet (author)
Lataniotis, LazarosQueen Mary University (author)
An Hashim, NikmanImperial College London (author)
Besse, CélineCentre National de Génotypage (author)
Boland, AnneCentre National de Génotypage (author)
Braund, Peter SUniversity of Leicester,Imperial College London (author)
Connell, John MUniversity of Dundee (author)
Dominiczak, AnnaUniversity of Glasgow (author)
Farmaki, Aliki-EleniNational and Kapodistrian University of Athens (author)
Franks, StephenImperial College London (author)
Grallert, HaraldGerman Center for Diabetes Research (author)
Jansson, Jan-HåkanUmeå University,Umeå universitet,Medicin(Swepub:umu)jaja0006 (author)
Karaleftheri, MariaEchinos Medical Centre (author)
Keinänen-Kiukaanniemi, SirkkaUniversity of Oulu (author)
Matchan, AngelaWellcome Trust Sanger Institute (author)
Pasko, DorotaUniversity of Exeter (author)
Peters, AnnetteHelmholtz Zentrum München (author)
Poulter, NeilImperial College London (author)
Rayner, Nigel WWellcome Trust Sanger Institute (author)
Renström, FridaLund University,Lunds universitet,Umeå universitet,Enheten för biobanksforskning,Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö , Sweden,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Queen Mary University(Swepub:lu)med-frm (author)
Rolandsson, OlovUmeå University,Umeå universitet,Allmänmedicin(Swepub:umu)olro0005 (author)
Sabater-Lleal, MariaKarolinska Institutet (author)
Sennblad, BengtKarolinska Institutet (author)
Sever, Peter (author)
Shields, DenisUniversity College Dublin (author)
Silveira, AngelaKarolinska Institutet (author)
Stanton, Alice VRoyal College of Surgeons in Ireland (author)
Strauch, KonstantinHelmholtz Zentrum München (author)
Tomaszewski, MaciejUniversity of Leicester (author)
Tsafantakis, EmmanouilAnogia Medical Centre (author)
Waldenberger, MelanieHelmholtz Zentrum München (author)
Blakemore, Alexandra I FImperial College London (author)
Dedoussis, George (author)
Escher, Stefan ALund University (author)
Kooner, Jaspal SEaling Hospital (author)
McCarthy, Mark IUniversity of Oxford (author)
Palmer, Colin N AUniversity of Dundee (author)
Hamsten, AndersKarolinska Institutet (author)
Caulfield, Mark JQueen Mary University (author)
Frayling, Timothy MUniversity of Exeter (author)
Tobin, Martin DUniversity of Leicester (author)
Jarvelin, Marjo-RiittaImperial College London (author)
Zeggini, EleftheriaWellcome Trust Sanger Institute (author)
Gieger, ChristianHelmholtz Zentrum München (author)
Chambers, John CImperial College London (author)
Wareham, Nick JQueen Mary University (author)
Munroe, Patricia BQueen Mary University (author)
Franks, Paul W.Umeå University,Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Harvard University(Swepub:lu)med-plf (author)
Samani, Nilesh JUniversity of Leicester (author)
Deloukas, PanosQueen Mary University (author)
Queen Mary UniversityUniversity of Leicester (creator_code:org_t)

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In:Human Molecular Genetics: Oxford University Press (OUP)25:18, s. 4094-41060964-69061460-2083

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By the author/editor: Kanoni, Stavroul ...; Masca, Nicholas ...; Stirrups, Kathle ...; Varga, Tibor V.; Warren, Helen R; Scott, Robert A; show more...; Southam, Lorrain ...; Zhang, Weihua; Yaghootkar, Hani ...; Müller-Nurasyid, ...; Couto Alves, Ale ...; Strawbridge, Ron ...; Lataniotis, Laza ...; An Hashim, Nikma ...; Besse, Céline; Boland, Anne; Braund, Peter S; Connell, John M; Dominiczak, Anna; Farmaki, Aliki-E ...; Franks, Stephen; Grallert, Harald; Jansson, Jan-Håk ...; Karaleftheri, Ma ...; Keinänen-Kiukaan ...; Matchan, Angela; Pasko, Dorota; Peters, Annette; Poulter, Neil; Rayner, Nigel W; Renström, Frida; Rolandsson, Olov; Sabater-Lleal, M ...; Sennblad, Bengt; Sever, Peter; Shields, Denis; Silveira, Angela; Stanton, Alice V; Strauch, Konstan ...; Tomaszewski, Mac ...; Tsafantakis, Emm ...; Waldenberger, Me ...; Blakemore, Alexa ...; Dedoussis, Georg ...; Escher, Stefan A; Kooner, Jaspal S; McCarthy, Mark I; Palmer, Colin N ...; Hamsten, Anders; Caulfield, Mark ...; Frayling, Timoth ...; Tobin, Martin D; Jarvelin, Marjo- ...; Zeggini, Elefthe ...; Gieger, Christia ...; Chambers, John C; Wareham, Nick J; Munroe, Patricia ...; Franks, Paul W.; Samani, Nilesh J; Deloukas, Panos; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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