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dc.contributor.authorLaw, PJen_US
dc.contributor.authorSud, Aen_US
dc.contributor.authorMitchell, JSen_US
dc.contributor.authorHenrion, Men_US
dc.contributor.authorOrlando, Gen_US
dc.contributor.authorLenive, Oen_US
dc.contributor.authorBroderick, Pen_US
dc.contributor.authorSpeedy, HEen_US
dc.contributor.authorJohnson, DCen_US
dc.contributor.authorKaiser, Men_US
dc.contributor.authorWeinhold, Nen_US
dc.contributor.authorCooke, Ren_US
dc.contributor.authorSunter, NJen_US
dc.contributor.authorJackson, GHen_US
dc.contributor.authorSummerfield, Gen_US
dc.contributor.authorHarris, RJen_US
dc.contributor.authorPettitt, ARen_US
dc.contributor.authorAllsup, DJen_US
dc.contributor.authorCarmichael, Jen_US
dc.contributor.authorBailey, JRen_US
dc.contributor.authorPratt, Gen_US
dc.contributor.authorRahman, Ten_US
dc.contributor.authorPepper, Cen_US
dc.contributor.authorFegan, Cen_US
dc.contributor.authorvon Strandmann, EPen_US
dc.contributor.authorEngert, Aen_US
dc.contributor.authorFörsti, Aen_US
dc.contributor.authorChen, Ben_US
dc.contributor.authorFilho, MIDSen_US
dc.contributor.authorThomsen, Hen_US
dc.contributor.authorHoffmann, Pen_US
dc.contributor.authorNoethen, MMen_US
dc.contributor.authorEisele, Len_US
dc.contributor.authorJöckel, K-Hen_US
dc.contributor.authorAllan, JMen_US
dc.contributor.authorSwerdlow, AJen_US
dc.contributor.authorGoldschmidt, Hen_US
dc.contributor.authorCatovsky, Den_US
dc.contributor.authorMorgan, GJen_US
dc.contributor.authorHemminki, Ken_US
dc.contributor.authorHoulston, RSen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2017-01-27T13:27:27Z
dc.date.issued2017-01-23en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28112199en_US
dc.identifiersrep41071en_US
dc.identifier.citationSci Rep, 2017, 7 pp. 41071 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/393
dc.identifier.eissn2045-2322en_US
dc.identifier.doi10.1038/srep41071en_US
dc.description.abstractB-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10-9) with opposing effects between CLL (P = 1.97 × 10-8) and HL (P = 3.31 × 10-3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10-12) was associated with increased CLL and HL risk (P = 4.68 × 10-12), and reduced MM risk (P = 1.12 × 10-2), and Gly70 in HLA-DQB1 (P = 3.15 × 10-10) showed opposing effects between CLL (P = 3.52 × 10-3) and HL (P = 3.41 × 10-9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs.en_US
dc.format.extent41071 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectAdaptor Proteins, Signal Transducingen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectFemaleen_US
dc.subjectGenetic Pleiotropyen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectHLA-DQ beta-Chainsen_US
dc.subjectHLA-DRB1 Chainsen_US
dc.subjectHodgkin Diseaseen_US
dc.subjectHumansen_US
dc.subjectLeukemia, Lymphocytic, Chronic, B-Cellen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectMultiple Myelomaen_US
dc.subjectOncogene Proteinsen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectRisk Factorsen_US
dc.titleGenome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-12-14en_US
rioxxterms.versionofrecord10.1038/srep41071en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2017-01-23en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfSci Repen_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.publication-statusPublished onlineen_US
pubs.volume7en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamAetiological Epidemiologyen_US
icr.researchteamMolecular & Population Geneticsen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorLaw, Philipen_US
dc.contributor.icrauthorSud, Amiten_US
dc.contributor.icrauthorHoulston, Richarden_US
dc.contributor.icrauthorOrlando, Giuliaen_US
dc.contributor.icrauthorBroderick, Peteren_US
dc.contributor.icrauthorJohnson, Daviden_US
dc.contributor.icrauthorKaiser, Martinen_US
dc.contributor.icrauthorSwerdlow, Anthonyen_US


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