Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorKanoni, S-
dc.contributor.authorMasca, NGD-
dc.contributor.authorStirrups, KE-
dc.contributor.authorVarga, TV-
dc.contributor.authorWarren, HR-
dc.contributor.authorScott, RA-
dc.contributor.authorSoutham, L-
dc.contributor.authorZhang, W-
dc.contributor.authorYaghootkar, H-
dc.contributor.authorMüller-Nurasyid, M-
dc.contributor.authorCouto Alves, A-
dc.contributor.authorStrawbridge, RJ-
dc.contributor.authorLataniotis, L-
dc.contributor.authorAn Hashim, N-
dc.contributor.authorBesse, C-
dc.contributor.authorBoland, A-
dc.contributor.authorBraund, PS-
dc.contributor.authorConnell, JM-
dc.contributor.authorDominiczak, A-
dc.contributor.authorFarmaki, A-E-
dc.contributor.authorFranks, S-
dc.contributor.authorGrallert, H-
dc.contributor.authorJansson, J-H-
dc.contributor.authorKaraleftheri, M-
dc.contributor.authorKeinänen-Kiukaanniemi, S-
dc.contributor.authorMatchan, A-
dc.contributor.authorPasko, D-
dc.contributor.authorPeters, A-
dc.contributor.authorPoulter, N-
dc.contributor.authorRayner, NW-
dc.contributor.authorRenström, F-
dc.contributor.authorRolandsson, O-
dc.contributor.authorSabater-Lleal, M-
dc.contributor.authorSennblad, B-
dc.contributor.authorSever, P-
dc.contributor.authorShields, D-
dc.contributor.authorSilveira, A-
dc.contributor.authorStanton, AV-
dc.contributor.authorStrauch, K-
dc.contributor.authorTomaszewski, M-
dc.contributor.authorTsafantakis, E-
dc.contributor.authorWaldenberger, M-
dc.contributor.authorBlakemore, AIF-
dc.contributor.authorDedoussis, G-
dc.contributor.authorEscher, SA-
dc.contributor.authorKooner, JS-
dc.contributor.authorMcCarthy, MI-
dc.contributor.authorPalmer, CNA-
dc.contributor.authorWellcome Trust Case Control Consortium-
dc.contributor.authorHamsten, A-
dc.contributor.authorCaulfield, MJ-
dc.contributor.authorFrayling, TM-
dc.contributor.authorTobin, MD-
dc.contributor.authorJarvelin, M-R-
dc.contributor.authorZeggini, E-
dc.contributor.authorGieger, C-
dc.contributor.authorChambers, JC-
dc.contributor.authorWareham, NJ-
dc.contributor.authorMunroe, PB-
dc.contributor.authorFranks, PW-
dc.contributor.authorSamani, NJ-
dc.contributor.authorDeloukas, P-
dc.identifier.citationHuman Molecular Genetics, 2016, 25 (18), pp. 4094-4106en
dc.descriptionSupplementary Material is available at HMG online.en
dc.description.abstractIt 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.en
dc.description.sponsorship1958BC was funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. This work forms part of the research themes contributing to the translational research portfolio of Barts Cardiovascular Biomedical Research Unit which is supported and funded by the National Institute for Health Research. PD is supported by British Heart Foundation grant RG/14/5/30893. ASCOT was supported by Pfizer, New York, NY, USA, Servier Research Group, Paris, France and by Leo Laboratories, Copenhagen, Denmark. BRIGHT was supported by the Medical Research Council of Great Britain (grant number G9521010D), the British Heart Foundation (grant number PG/02/128) and the Wellcome Trust Strategic Awards 083948A and 085475. AFD was supported by the British Heart Foundation (grant numbers RG/07/005/23633, SP/08/005/25115); and by the European Union Ingenious HyperCare Consortium: Integrated Genomics, Clinical Research, and Care in Hypertension (grant number LSHM-C7-2006-037093). DIABNORD was funded by Novo Nordisk, the Swedish Research Council, Påhlssons Foundation, the Swedish Heart Lung Foundation, and the Skåne Regional Health Authority (all to PWF). The EFSOCH study was supported by South West NHS Research and Development, Exeter NHS Research and Development, the Darlington Trust, and the Peninsula NIHR Clinical Research Facility at the University of Exeter. Timothy Frayling is supported by the European Research Council grant: SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC. EPIC and EPIC-Norfolk is supported by the Medical Research Council programme grants (G0401527, G1000143) and Cancer Research UK programme grant (C864/A8257). The Fenland Study is funded by the Medical Research Council (MC_U106179471). FIA3 was supported in part by a grant from the Swedish Heart-Lung Foundation (grant no. 2020389 to PW Franks). GLACIER was funded by Novo Nordisk, the Swedish Research Council, Påhlssons Foundation, the Swedish Heart Lung Foundation, and the Skåne Regional Health Authority (all to PWF). GoDARTS was supported by the Wellcome Trust (Wellcome Trust UK Type 2 Diabetes Case Control Collection) and the Scottish Health Informatics Programme. The Chief Scientist Office supported informatics. Project funded by the UK Medical Research Council (G0601261). GRAPHIC exome array genotyping was funded by the NIHR and the Wellcome Trust. NJS holds a Chair funded by the British Heart Foundation and is a NIHR Senior Investigator. NM is funded by the NIHR Leicester Cardiovascular Biomedical Research Unit. The GRAPHIC Study is part of the portfolio of studies supported by the NIHR Leicester Cardiovascular BRU. HELICMANOLIS and HELICPomak were funded by the Wellcome Trust (098051) and the European Research Council (ERC-2011-StG 280559-SEPI). KORA was funded by the German Federal Ministry of Education and Research and by the State of Bavaria, DZHK (German Centre for Cardiovascular Research) and the BMBF (German Ministry of Education and Research). LOLIPOP is supported by the National Institute for Health Research (NIHR), the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966,G0700931), the Wellcome Trust (084723/Z/08/Z) the NIHR (RP-PG-0407-10371), European Union FP7 (EpiMigrant, 279143) and Action on Hearing Loss (G51). NFBC1986: was supported by the Academy of Finland (project grants 104781, 120315, 129269, 1114194, Center of Excellence in Complex Disease Genetics and SALVE), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), the Medical Research Council, UK (G0500539, G0600705, PrevMetSyn/SALVE) and the Wellcome Trust (project grant GR069224), UK, ENGAGE project and grant agreement HEALTH-F4-2007-201413, and the EU Framework Programme 7 small-scale focused research collaborative project EurHEALTHAgeing 277849. SCARF was funded by the Foundation for Strategic Research, the Swedish Heart-Lung Foundation, the Swedish Research Council (8691, 12660, 20653), the European Commission (LSHM-CT-2007-037273), the Knut and Alice Wallenberg Foundation, the Torsten and Ragnar Söderberg Foundation, the Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and the Stockholm County Council, and the Stockholm County Council (560183). BS acknowledge funding from the Magnus Bergvall Foundation and the Foundation for Old Servants. MF acknowledge funding from the Swedish e-Science Research Center (SeRC).en
dc.publisherOxford University Press (OUP)en
dc.rightsCopyright © 2016, Oxford University Press (OUP). Deposited with reference to the publisher’s open access archiving policy. (
dc.subjectCholesterol, HDLen
dc.subjectCholesterol, LDLen
dc.subjectEuropean Continental Ancestry Groupen
dc.subjectGene Frequencyen
dc.subjectGenome-Wide Association Studyen
dc.subjectLipid Metabolismen
dc.subjectMiddle Ageden
dc.subjectPolymorphism, Single Nucleotideen
dc.titleAnalysis with the exome array identifies multiple new independent variants in lipid loci.en
dc.typeJournal Articleen
dc.type.subtypeJournal Article;Research Support, Non-U.S. Gov't;Research Support, N.I.H., Extramural-
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCESen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciencesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciencesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Cardiovascularen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Genome Scienceen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Populationen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Respiratory Scienceen
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

Files in This Item:
File Description SizeFormat 
Kanoni Analysis with the exome array identifies multiple new independent variants in lipid loci 2016 Accepted.pdfPost-review (final submitted author manuscript)235.33 kBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.