dc.contributor.author | Law, PJ | |
dc.contributor.author | Sud, A | |
dc.contributor.author | Mitchell, JS | |
dc.contributor.author | Henrion, M | |
dc.contributor.author | Orlando, G | |
dc.contributor.author | Lenive, O | |
dc.contributor.author | Broderick, P | |
dc.contributor.author | Speedy, HE | |
dc.contributor.author | Johnson, DC | |
dc.contributor.author | Kaiser, M | |
dc.contributor.author | Weinhold, N | |
dc.contributor.author | Cooke, R | |
dc.contributor.author | Sunter, NJ | |
dc.contributor.author | Jackson, GH | |
dc.contributor.author | Summerfield, G | |
dc.contributor.author | Harris, RJ | |
dc.contributor.author | Pettitt, AR | |
dc.contributor.author | Allsup, DJ | |
dc.contributor.author | Carmichael, J | |
dc.contributor.author | Bailey, JR | |
dc.contributor.author | Pratt, G | |
dc.contributor.author | Rahman, T | |
dc.contributor.author | Pepper, C | |
dc.contributor.author | Fegan, C | |
dc.contributor.author | von Strandmann, EP | |
dc.contributor.author | Engert, A | |
dc.contributor.author | Försti, A | |
dc.contributor.author | Chen, B | |
dc.contributor.author | Filho, MIDS | |
dc.contributor.author | Thomsen, H | |
dc.contributor.author | Hoffmann, P | |
dc.contributor.author | Noethen, MM | |
dc.contributor.author | Eisele, L | |
dc.contributor.author | Jöckel, K-H | |
dc.contributor.author | Allan, JM | |
dc.contributor.author | Swerdlow, AJ | |
dc.contributor.author | Goldschmidt, H | |
dc.contributor.author | Catovsky, D | |
dc.contributor.author | Morgan, GJ | |
dc.contributor.author | Hemminki, K | |
dc.contributor.author | Houlston, RS | |
dc.date.accessioned | 2017-01-27T13:27:27Z | |
dc.date.issued | 2017-01-23 | |
dc.identifier.citation | Scientific reports, 2017, 7 pp. 41071 - ? | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/393 | |
dc.identifier.eissn | 2045-2322 | |
dc.identifier.doi | 10.1038/srep41071 | |
dc.description.abstract | B-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. | |
dc.format | Electronic | |
dc.format.extent | 41071 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Hodgkin Disease | |
dc.subject | Multiple Myeloma | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | Oncogene Proteins | |
dc.subject | Risk Factors | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Leukemia, Lymphocytic, Chronic, B-Cell | |
dc.subject | Genome-Wide Association Study | |
dc.subject | Genetic Pleiotropy | |
dc.subject | HLA-DQ beta-Chains | |
dc.subject | HLA-DRB1 Chains | |
dc.title | Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-12-14 | |
rioxxterms.versionofrecord | 10.1038/srep41071 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-01-23 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Scientific reports | |
pubs.notes | No embargo | |
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/Cancer Genomics | |
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.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/Cancer Genomics | |
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-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Aetiological Epidemiology | |
icr.researchteam | Cancer Genomics | |
icr.researchteam | Molecular & Population Genetics | |
icr.researchteam | Myeloma Group | |
dc.contributor.icrauthor | Law, Philip | |
dc.contributor.icrauthor | Sud, Amit | |
dc.contributor.icrauthor | Orlando, Giulia | |
dc.contributor.icrauthor | Broderick, Peter | |
dc.contributor.icrauthor | Johnson, David | |
dc.contributor.icrauthor | Kaiser, Martin | |
dc.contributor.icrauthor | Swerdlow, Anthony | |
dc.contributor.icrauthor | Houlston, Richard | |