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

Molly Went; Amit Sud; Helen Speedy; Nicola J. Sunter; Asta Försti; Philip J. Law; David C. Johnson; Fabio Mirabella; Amy Holroyd; Ni Li; Giulia Orlando; Niels Weinhold; Mark van Duin; Bowang Chen; Jonathan S. Mitchell; Larry Mansouri; Gunnar Juliusson; Karin E. Smedby; Sandrine Jayne; Aneela Majid; Claire Dearden; David J. Allsup; James R. Bailey; Guy Pratt; Chris Pepper; Chris Fegan; Richard Rosenquist; Rowan Kuiper; Owen W. Stephens; Uta Bertsch; Peter Broderick; Hermann Einsele; Walter M. Gregory; Jens Hillengass; Per Hoffmann; Graham H. Jackson; Karl Heinz Jöckel; Jolanta Nickel; Markus M. Nöthen; Miguel Inacio da Silva Filho; Hauke Thomsen; Brian A. Walker; Annemiek Broyl; Faith E. Davies; Markus Hansson; Hartmut Goldschmidt; Martin J.S. Dyer; Martin Kaiser; Pieter Sonneveld; Gareth J. Morgan; Kari Hemminki; Björn Nilsson; Daniel Catovsky; James M. Allan; Richard S. Houlston

doi:10.1038/s41408-018-0162-8

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

Molly Went, Amit Sud, Helen Speedy, Nicola J. Sunter, Asta Försti, Philip J. Law, David C. Johnson, Fabio Mirabella, Amy Holroyd, Ni Li, Giulia Orlando, Niels Weinhold, Mark van Duin, Bowang Chen, Jonathan S. Mitchell, Larry Mansouri, Gunnar Juliusson, Karin E. Smedby, Sandrine Jayne, Aneela MajidClaire Dearden, David J. Allsup, James R. Bailey, Guy Pratt, Chris Pepper, Chris Fegan, Richard Rosenquist, Rowan Kuiper, Owen W. Stephens, Uta Bertsch, Peter Broderick, Hermann Einsele, Walter M. Gregory, Jens Hillengass, Per Hoffmann, Graham H. Jackson, Karl Heinz Jöckel, Jolanta Nickel, Markus M. Nöthen, Miguel Inacio da Silva Filho, Hauke Thomsen, Brian A. Walker, Annemiek Broyl, Faith E. Davies, Markus Hansson, Hartmut Goldschmidt, Martin J.S. Dyer, Martin Kaiser, Pieter Sonneveld, Gareth J. Morgan, Kari Hemminki, Björn Nilsson, Daniel Catovsky, James M. Allan, Richard S. Houlston

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	1
Journal	Blood Cancer Journal
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41408-018-0162-8
Publication status	Published - 2018 Dec 21

Subject classification (UKÄ)

Cancer and Oncology
Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41408-018-0162-8

Genetic predisposition for multiple myeloma
Nilsson, B. (PI), Pertesi, M. (Researcher), Ajore, R. (Researcher), Wihlborg, A.-K. (Researcher), Duran Lozano, L. (Researcher), Cafaro, C. (Researcher), Johnsson, E. (Researcher), Hansson, M. (Researcher), Halvarsson, B.-M. (Researcher) & Niroula, A. (Researcher)
2011/01/03 → …
Project: Research

Cite this

Went, M., Sud, A., Speedy, H., Sunter, N. J., Försti, A., Law, P. J., Johnson, D. C., Mirabella, F., Holroyd, A., Li, N., Orlando, G., Weinhold, N., van Duin, M., Chen, B., Mitchell, J. S., Mansouri, L., Juliusson, G., Smedby, K. E., Jayne, S., ... Houlston, R. S. (2018). Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology. Blood Cancer Journal, 9(1), Article 1. https://doi.org/10.1038/s41408-018-0162-8

@article{d988e129692a4219841d8b4796297a5f,

title = "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.",

author = "Molly Went and Amit Sud and Helen Speedy and Sunter, {Nicola J.} and Asta F{\"o}rsti and Law, {Philip J.} and Johnson, {David C.} and Fabio Mirabella and Amy Holroyd and Ni Li and Giulia Orlando and Niels Weinhold and {van Duin}, Mark and Bowang Chen and Mitchell, {Jonathan S.} and Larry Mansouri and Gunnar Juliusson and Smedby, {Karin E.} and Sandrine Jayne and Aneela Majid and Claire Dearden and Allsup, {David J.} and Bailey, {James R.} and Guy Pratt and Chris Pepper and Chris Fegan and Richard Rosenquist and Rowan Kuiper and Stephens, {Owen W.} and Uta Bertsch and Peter Broderick and Hermann Einsele and Gregory, {Walter M.} and Jens Hillengass and Per Hoffmann and Jackson, {Graham H.} and J{\"o}ckel, {Karl Heinz} and Jolanta Nickel and N{\"o}then, {Markus M.} and {da Silva Filho}, {Miguel Inacio} and Hauke Thomsen and Walker, {Brian A.} and Annemiek Broyl and Davies, {Faith E.} and Markus Hansson and Hartmut Goldschmidt and Dyer, {Martin J.S.} and Martin Kaiser and Pieter Sonneveld and Morgan, {Gareth J.} and Kari Hemminki and Bj{\"o}rn Nilsson and Daniel Catovsky and Allan, {James M.} and Houlston, {Richard S.}",

year = "2018",

month = dec,

day = "21",

doi = "10.1038/s41408-018-0162-8",

language = "English",

volume = "9",

journal = "Blood Cancer Journal",

issn = "2044-5385",

publisher = "Nature Publishing Group",

number = "1",

}

Went, M, Sud, A, Speedy, H, Sunter, NJ, Försti, 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, Jöckel, KH, Nickel, J, Nöthen, 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 2018, 'Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology', Blood Cancer Journal, vol. 9, no. 1, 1. https://doi.org/10.1038/s41408-018-0162-8

TY - JOUR

T1 - Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology

AU - Went, Molly

AU - Sud, Amit

AU - Speedy, Helen

AU - Sunter, Nicola J.

AU - Försti, Asta

AU - Law, Philip J.

AU - Johnson, David C.

AU - Mirabella, Fabio

AU - Holroyd, Amy

AU - Li, Ni

AU - Orlando, Giulia

AU - Weinhold, Niels

AU - van Duin, Mark

AU - Chen, Bowang

AU - Mitchell, Jonathan S.

AU - Mansouri, Larry

AU - Juliusson, Gunnar

AU - Smedby, Karin E.

AU - Jayne, Sandrine

AU - Majid, Aneela

AU - Dearden, Claire

AU - Allsup, David J.

AU - Bailey, James R.

AU - Pratt, Guy

AU - Pepper, Chris

AU - Fegan, Chris

AU - Rosenquist, Richard

AU - Kuiper, Rowan

AU - Stephens, Owen W.

AU - Bertsch, Uta

AU - Broderick, Peter

AU - Einsele, Hermann

AU - Gregory, Walter M.

AU - Hillengass, Jens

AU - Hoffmann, Per

AU - Jackson, Graham H.

AU - Jöckel, Karl Heinz

AU - Nickel, Jolanta

AU - Nöthen, Markus M.

AU - da Silva Filho, Miguel Inacio

AU - Thomsen, Hauke

AU - Walker, Brian A.

AU - Broyl, Annemiek

AU - Davies, Faith E.

AU - Hansson, Markus

AU - Goldschmidt, Hartmut

AU - Dyer, Martin J.S.

AU - Kaiser, Martin

AU - Sonneveld, Pieter

AU - Morgan, Gareth J.

AU - Hemminki, Kari

AU - Nilsson, Björn

AU - Catovsky, Daniel

AU - Allan, James M.

AU - Houlston, Richard S.

PY - 2018/12/21

Y1 - 2018/12/21

N2 - 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.

AB - 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.

U2 - 10.1038/s41408-018-0162-8

DO - 10.1038/s41408-018-0162-8

M3 - Article

C2 - 30602759

AN - SCOPUS:85059502420

SN - 2044-5385

VL - 9

JO - Blood Cancer Journal

JF - Blood Cancer Journal

IS - 1

M1 - 1

ER -

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

Abstract

Subject classification (UKÄ)

UN SDGs

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Genetic predisposition for multiple myeloma

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