dc.contributor.author | Ajore, R | |
dc.contributor.author | Niroula, A | |
dc.contributor.author | Pertesi, M | |
dc.contributor.author | Cafaro, C | |
dc.contributor.author | Thodberg, M | |
dc.contributor.author | Went, M | |
dc.contributor.author | Bao, EL | |
dc.contributor.author | Duran-Lozano, L | |
dc.contributor.author | Lopez de Lapuente Portilla, A | |
dc.contributor.author | Olafsdottir, T | |
dc.contributor.author | Ugidos-Damboriena, N | |
dc.contributor.author | Magnusson, O | |
dc.contributor.author | Samur, M | |
dc.contributor.author | Lareau, CA | |
dc.contributor.author | Halldorsson, GH | |
dc.contributor.author | Thorleifsson, G | |
dc.contributor.author | Norddahl, GL | |
dc.contributor.author | Gunnarsdottir, K | |
dc.contributor.author | Försti, A | |
dc.contributor.author | Goldschmidt, H | |
dc.contributor.author | Hemminki, K | |
dc.contributor.author | van Rhee, F | |
dc.contributor.author | Kimber, S | |
dc.contributor.author | Sperling, AS | |
dc.contributor.author | Kaiser, M | |
dc.contributor.author | Anderson, K | |
dc.contributor.author | Jonsdottir, I | |
dc.contributor.author | Munshi, N | |
dc.contributor.author | Rafnar, T | |
dc.contributor.author | Waage, A | |
dc.contributor.author | Weinhold, N | |
dc.contributor.author | Thorsteinsdottir, U | |
dc.contributor.author | Sankaran, VG | |
dc.contributor.author | Stefansson, K | |
dc.contributor.author | Houlston, R | |
dc.contributor.author | Nilsson, B | |
dc.date.accessioned | 2022-02-23T14:19:38Z | |
dc.date.available | 2022-02-23T14:19:38Z | |
dc.date.issued | 2022-01-10 | |
dc.identifier.citation | Nature communications, 2022, 13 (1), pp. 151 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5036 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-021-27666-x | |
dc.identifier.doi | 10.1038/s41467-021-27666-x | |
dc.description.abstract | Thousands of non-coding variants have been associated with increased risk of human diseases, yet the causal variants and their mechanisms-of-action remain obscure. In an integrative study combining massively parallel reporter assays (MPRA), expression analyses (eQTL, meQTL, PCHiC) and chromatin accessibility analyses in primary cells (caQTL), we investigate 1,039 variants associated with multiple myeloma (MM). We demonstrate that MM susceptibility is mediated by gene-regulatory changes in plasma cells and B-cells, and identify putative causal variants at six risk loci (SMARCD3, WAC, ELL2, CDCA7L, CEP120, and PREX1). Notably, three of these variants co-localize with significant plasma cell caQTLs, signaling the presence of causal activity at these precise genomic positions in an endogenous chromosomal context in vivo. Our results provide a systematic functional dissection of risk loci for a hematologic malignancy. | |
dc.format | Electronic | |
dc.format.extent | 151 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | B-Lymphocytes | |
dc.subject | Plasma Cells | |
dc.subject | Chromatin | |
dc.subject | Humans | |
dc.subject | Multiple Myeloma | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | Guanine Nucleotide Exchange Factors | |
dc.subject | Cell Cycle Proteins | |
dc.subject | Neoplasm Proteins | |
dc.subject | Chromosomal Proteins, Non-Histone | |
dc.subject | Repressor Proteins | |
dc.subject | Transcriptional Elongation Factors | |
dc.subject | DNA, Intergenic | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Risk Assessment | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Base Sequence | |
dc.subject | Inheritance Patterns | |
dc.subject | Polymorphism, Genetic | |
dc.subject | Quantitative Trait Loci | |
dc.subject | Primary Cell Culture | |
dc.title | Functional dissection of inherited non-coding variation influencing multiple myeloma risk. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-12-02 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-021-27666-x | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2022-01-10 | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not known | |
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/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Myeloma Molecular Therapy | |
pubs.publication-status | Published | |
pubs.volume | 13 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Genomics | |
icr.researchteam | Myeloma Molecular Therapy | |
dc.contributor.icrauthor | Went, Molly | |
dc.contributor.icrauthor | Kaiser, Martin | |
dc.contributor.icrauthor | Houlston, Richard | |