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

Abstract

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.

Metadata

Item Type:	Article
Authors/Creators:	Went, M Sud, A Speedy, H Sunter, NJ Foersti, 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 https://orcid.org/0000-0003-2641-8416 Hillengass, J Hoffmann, P Jackson, GH Joeckel, K-H Nickel, J Noethen, MM da Silva Filho, MI Thomsen, H Walker, BA Broyl, A Davies, FE Hansson, M Goldschmidt, H Dyer, MJS Kaiser, MJS Sonneveld, P Morgan, GJ Hemminki, K Nilsson, B Catovsky, D Allan, JM Houlston, RS
Copyright, Publisher and Additional Information:	© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 19 November 2018 Published (online): 21 December 2018 Published: 21 December 2018
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Clinical Trials Research (LICTR) (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	22 Jan 2019 12:52
Last Modified:	22 Jan 2019 12:52
Status:	Published
Publisher:	Springer Nature
Identification Number:	10.1038/s41408-018-0162-8
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:141380

CORE (COnnecting REpositories)

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

Abstract

Metadata

Download

Published Version

External copy

Export

Statistics