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Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology

Lookup NU author(s): Dr Nicola Sunter, Professor Graham Jackson, Professor James Allan

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Abstract

© 2018, The Author(s). 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 (Rg = 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 ChIP-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.

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Author(s): Went M, Sud A, Speedy H, Sunter NJ, Forsti A, Law PJ, Johnson DC, Mirabella F, Holroyd A, Li N, Orlando G, Weinhold N, van Duin M, Chen B, Mitchell JS, Mansouri L, Juliusson G, Smedby KE, Jayne S, Majid A, Dearden C, Allsup DJ, Bailey JR, Pratt G, Pepper C, Fegan C, Rosenquist R, Kuiper R, Stephens OW, Bertsch U, Broderick P, Einsele H, Gregory WM, Hillengass J, Hoffmann P, Jackson GH, Jockel K-H, Nickel J, Nothen MM, da Silva Filho MI, Thomsen H, Walker BA, Broyl A, Davies FE, Hansson M, Goldschmidt H, Dyer MJS, Kaiser M, Sonneveld P, Morgan GJ, Hemminki K, Nilsson B, Catovsky D, Allan JM, Houlston RS

Publication type: Article

Publication status: Published

Journal: Blood Cancer Journal

Year: 2019

Volume: 9

Issue: 1

Online publication date: 21/12/2018

Acceptance date: 19/11/2018

Date deposited: 18/01/2019

ISSN (print): 2044-5385

ISSN (electronic): 2044-5385

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41408-018-0162-8

DOI: 10.1038/s41408-018-0162-8

PubMed id: 30602759

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