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Blood Cancer J. 2018 Dec 21;9(1):1. doi: 10.1038/s41408-018-0162-8.

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

Author information

1
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK. molly.went@icr.ac.uk.
2
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
3
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
4
German Cancer Research Center, 69120, Heidelberg, Germany.
5
Center for Primary Health Care Research, Lund University, SE-205 02, Malmo, Sweden.
6
Division of Molecular Pathology, The Institute of Cancer Research, London, SW7 3RP, UK.
7
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
8
Department of Internal Medicine V, University of Heidelberg, 69117, Heidelberg, Germany.
9
Department of Hematology, Erasmus MC Cancer Institute, 3075 EA, Rotterdam, The Netherlands.
10
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 75105, Uppsala, Sweden.
11
Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Hematology and Transplantation, Lund University, Lund, Sweden.
12
Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
13
Ernest and Helen Scott Haematological Research Institute, Leicester University, Leicester, UK.
14
Department of Haematology, Hull Royal Infirmary, Hull, UK.
15
Hull York Medical School and University of Hull, Hull, UK.
16
Department of Haematology, Birmingham Heartlands Hospital, Birmingham, UK.
17
Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.
18
Cardiff and Vale National Health Service Trust, Heath Park, Cardiff, UK.
19
National Centre of Tumor Diseases, 69120, Heidelberg, Germany.
20
University Clinic of Würzburg, 97080, Würzburg, Germany.
21
Clinical Trials Research Unit, University of Leeds, Leeds, LS2 9PH, UK.
22
Institute of Human Genetics, University of Bonn, D-53127, Bonn, Germany.
23
Division of Medical Genetics, Department of Biomedicine, University of Basel, 4003, Basel, Switzerland.
24
Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK.
25
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
26
Department of Genomics, Life and Brain Center, University of Bonn, D-53127, Bonn, Germany.
27
Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, SE-221 84 Lund University, Lund, Sweden.
28
Broad Institute, 7 Cambridge Center, Cambridge, MA, 02142, USA.

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.

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