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Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.
Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.ORCID iD: 0000-0002-6133-0164
Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.
Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
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2018 (English)In: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 9, article id 1Article in journal (Refereed) Published
Abstract [en]

The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (R-g = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChlP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.

Place, publisher, year, edition, pages
2018. Vol. 9, article id 1
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Hematology Cancer and Oncology
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URN: urn:nbn:se:uu:diva-374121DOI: 10.1038/s41408-018-0162-8ISI: 000454815100001PubMedID: 30602759OAI: oai:DiVA.org:uu-374121DiVA, id: diva2:1281973
Funder
Swedish Foundation for Strategic Research , KF10-0009Knut and Alice Wallenberg Foundation, 2012.0193Swedish Research Council, 2012-1753EU, FP7, Seventh Framework Programme, LSHC-Ct-2006-037602Marianne and Marcus Wallenberg FoundationAvailable from: 2019-01-23 Created: 2019-01-23 Last updated: 2019-01-23Bibliographically approved

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