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

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, Hillengass J, Hoffmann P, Jackson GH, Joeckel KH, Nickel J, Noethen 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 (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 9

Article Number: 1

Journal Issue: 1

DOI: 10.1038/s41408-018-0162-8

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 (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 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.

Involved external institutions

The Institute of Cancer Research (ICR) United Kingdom (GB) Newcastle University United Kingdom (GB) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of Arkansas United States (USA) (US) Erasmus University Medical Center (MC) Netherlands (NL) Uppsala University Sweden (SE) Lund University / Lunds universitet Sweden (SE) Karolinska Institute Sweden (SE) University of Leicester United Kingdom (GB) Hull York Medical School (HYMS) United Kingdom (GB) Heartlands Hospital United Kingdom (GB) Cardiff University United Kingdom (GB) Universitätsklinikum Würzburg Germany (DE) University of Leeds United Kingdom (GB) Ruprecht-Karls-Universität Heidelberg Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Royal Victoria Infirmary United Kingdom (GB) Universität Duisburg-Essen (UDE) Germany (DE) Hull and East Yorkshire Hospitals NHS Trust United Kingdom (GB) Cardiff and Vale University Health Board United Kingdom (GB)

How to cite

APA:

Went, M., Sud, A., Speedy, H., Sunter, N.J., Foersti, A., Law, P.J.,... Houlston, R.S. (2019). Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology. Blood Cancer Journal, 9(1). https://doi.org/10.1038/s41408-018-0162-8

MLA:

Went, Molly, et al. "Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology." Blood Cancer Journal 9.1 (2019).

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