Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

J.S. Mitchell; N. Li; N. Weinhold; A. Forsti; M. Ali; Duin M. van; G. Thorleifsson; D.C. Johnson; B. Chen; B.M. Halvarsson; D.F. Gudbjartsson; R. Kuiper; O.W. Stephens; U. Bertsch; P. Broderick; C. Campo; H. Einsele; W.A. Gregory; U. Gullberg; M. Henrion; J. Hillengass; P. Hoffmann; G.H. Jackson; E. Johnsson; M. Joud; S.Y. Kristinsson; S. Lenhoff; O. Lenive; U.H. Mellqvist; G. Migliorini; H. Nahi; S. Nelander; J. Nickel; M.M. Nothen; T. Rafnar; F.M. Ross; M.I. da Silva Filho; B. Swaminathan; H. Thomsen; I. Turesson; A. Vangsted; Ulla Birgitte Vogel; A. Waage; B.A. Walker; A.K. Wihlborg; A. Broyl; F.E. Davies; U. Thorsteinsdottir; C. Langer; M. Hansson; M. Kaiser; P. Sonneveld; K. Stefansson; G.J. Morgan; H. Goldschmidt; K. Hemminki; B. Nilsson; R.S. Houlston

doi:10.1038/ncomms12050

Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

J.S. Mitchell
, N. Li
, N. Weinhold
, A. Forsti
, M. Ali
, Duin M. van
, G. Thorleifsson
, D.C. Johnson
, B. Chen
, B.M. Halvarsson
, D.F. Gudbjartsson
, R. Kuiper
, O.W. Stephens
, U. Bertsch
, P. Broderick
, C. Campo
, H. Einsele
, W.A. Gregory
, U. Gullberg
, M. Henrion

J. Hillengass, P. Hoffmann, G.H. Jackson, E. Johnsson, M. Joud, S.Y. Kristinsson, S. Lenhoff, O. Lenive, U.H. Mellqvist, G. Migliorini, H. Nahi, S. Nelander, J. Nickel, M.M. Nothen, T. Rafnar, F.M. Ross, M.I. da Silva Filho, B. Swaminathan, H. Thomsen, I. Turesson, A. Vangsted, Ulla Birgitte Vogel, A. Waage, B.A. Walker, A.K. Wihlborg, A. Broyl, F.E. Davies, U. Thorsteinsdottir, C. Langer, M. Hansson, M. Kaiser, P. Sonneveld, K. Stefansson, G.J. Morgan, H. Goldschmidt, K. Hemminki, B. Nilsson, R.S. Houlston

Department of Chemistry and Microbiology

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

[Open access]Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 x 10(-8)), 6q21 (rs9372120, P=9.09 x 10(-15)), 7q36.1 (rs7781265, P=9.71 x 10(-9)), 8q24.21 (rs1948915, P=4.20 x 10(-11)), 9p21.3 (rs2811710, P=1.72 x 10(-13)), 10p12.1 (rs2790457, P=1.77 x 10(-8)), 16q23.1 (rs7193541, P=5.00 x 10(-12)) and 20q13.13 (rs6066835, P=1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development

Original language	English
Journal	Nature Communications
Volume	7
Pages (from-to)	12050-
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms12050
Publication status	Published - 2016

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Mitchell, J. S., Li, N., Weinhold, N., Forsti, A., Ali, M., van, D. M., Thorleifsson, G., Johnson, D. C., Chen, B., Halvarsson, B. M., Gudbjartsson, D. F., Kuiper, R., Stephens, O. W., Bertsch, U., Broderick, P., Campo, C., Einsele, H., Gregory, W. A., Gullberg, U., ... Houlston, R. S. (2016). Genome-wide association study identifies multiple susceptibility loci for multiple myeloma. Nature Communications, 7, 12050-. https://doi.org/10.1038/ncomms12050

@article{5d3edf0315284a87bd878889f5518ca9,

title = "Genome-wide association study identifies multiple susceptibility loci for multiple myeloma",

abstract = "[Open access]Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 x 10(-8)), 6q21 (rs9372120, P=9.09 x 10(-15)), 7q36.1 (rs7781265, P=9.71 x 10(-9)), 8q24.21 (rs1948915, P=4.20 x 10(-11)), 9p21.3 (rs2811710, P=1.72 x 10(-13)), 10p12.1 (rs2790457, P=1.77 x 10(-8)), 16q23.1 (rs7193541, P=5.00 x 10(-12)) and 20q13.13 (rs6066835, P=1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development",

author = "J.S. Mitchell and N. Li and N. Weinhold and A. Forsti and M. Ali and van, \{Duin M.\} and G. Thorleifsson and D.C. Johnson and B. Chen and B.M. Halvarsson and D.F. Gudbjartsson and R. Kuiper and O.W. Stephens and U. Bertsch and P. Broderick and C. Campo and H. Einsele and W.A. Gregory and U. Gullberg and M. Henrion and J. Hillengass and P. Hoffmann and G.H. Jackson and E. Johnsson and M. Joud and S.Y. Kristinsson and S. Lenhoff and O. Lenive and U.H. Mellqvist and G. Migliorini and H. Nahi and S. Nelander and J. Nickel and M.M. Nothen and T. Rafnar and F.M. Ross and \{da Silva Filho\}, M.I. and B. Swaminathan and H. Thomsen and I. Turesson and A. Vangsted and Vogel, \{Ulla Birgitte\} and A. Waage and B.A. Walker and A.K. Wihlborg and A. Broyl and F.E. Davies and U. Thorsteinsdottir and C. Langer and M. Hansson and M. Kaiser and P. Sonneveld and K. Stefansson and G.J. Morgan and H. Goldschmidt and K. Hemminki and B. Nilsson and R.S. Houlston",

note = "SUBMISSIONYEAR:2016",

year = "2016",

doi = "10.1038/ncomms12050",

language = "English",

volume = "7",

pages = "12050--",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Mitchell, JS, Li, N, Weinhold, N, Forsti, A, Ali, M, van, DM, Thorleifsson, G, Johnson, DC, Chen, B, Halvarsson, BM, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Einsele, H, Gregory, WA, Gullberg, U, Henrion, M, Hillengass, J, Hoffmann, P, Jackson, GH, Johnsson, E, Joud, M, Kristinsson, SY, Lenhoff, S, Lenive, O, Mellqvist, UH, Migliorini, G, Nahi, H, Nelander, S, Nickel, J, Nothen, MM, Rafnar, T, Ross, FM, da Silva Filho, MI, Swaminathan, B, Thomsen, H, Turesson, I, Vangsted, A, Vogel, UB, Waage, A, Walker, BA, Wihlborg, AK, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Goldschmidt, H, Hemminki, K, Nilsson, B & Houlston, RS 2016, 'Genome-wide association study identifies multiple susceptibility loci for multiple myeloma', Nature Communications, vol. 7, pp. 12050-. https://doi.org/10.1038/ncomms12050

TY - JOUR

T1 - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

AU - Mitchell, J.S.

AU - Li, N.

AU - Weinhold, N.

AU - Forsti, A.

AU - Ali, M.

AU - van, Duin M.

AU - Thorleifsson, G.

AU - Johnson, D.C.

AU - Chen, B.

AU - Halvarsson, B.M.

AU - Gudbjartsson, D.F.

AU - Kuiper, R.

AU - Stephens, O.W.

AU - Bertsch, U.

AU - Broderick, P.

AU - Campo, C.

AU - Einsele, H.

AU - Gregory, W.A.

AU - Gullberg, U.

AU - Henrion, M.

AU - Hillengass, J.

AU - Hoffmann, P.

AU - Jackson, G.H.

AU - Johnsson, E.

AU - Joud, M.

AU - Kristinsson, S.Y.

AU - Lenhoff, S.

AU - Lenive, O.

AU - Mellqvist, U.H.

AU - Migliorini, G.

AU - Nahi, H.

AU - Nelander, S.

AU - Nickel, J.

AU - Nothen, M.M.

AU - Rafnar, T.

AU - Ross, F.M.

AU - da Silva Filho, M.I.

AU - Swaminathan, B.

AU - Thomsen, H.

AU - Turesson, I.

AU - Vangsted, A.

AU - Vogel, Ulla Birgitte

AU - Waage, A.

AU - Walker, B.A.

AU - Wihlborg, A.K.

AU - Broyl, A.

AU - Davies, F.E.

AU - Thorsteinsdottir, U.

AU - Langer, C.

AU - Hansson, M.

AU - Kaiser, M.

AU - Sonneveld, P.

AU - Stefansson, K.

AU - Morgan, G.J.

AU - Goldschmidt, H.

AU - Hemminki, K.

AU - Nilsson, B.

AU - Houlston, R.S.

N1 - SUBMISSIONYEAR:2016

PY - 2016

Y1 - 2016

N2 - [Open access]Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 x 10(-8)), 6q21 (rs9372120, P=9.09 x 10(-15)), 7q36.1 (rs7781265, P=9.71 x 10(-9)), 8q24.21 (rs1948915, P=4.20 x 10(-11)), 9p21.3 (rs2811710, P=1.72 x 10(-13)), 10p12.1 (rs2790457, P=1.77 x 10(-8)), 16q23.1 (rs7193541, P=5.00 x 10(-12)) and 20q13.13 (rs6066835, P=1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development

AB - [Open access]Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 x 10(-8)), 6q21 (rs9372120, P=9.09 x 10(-15)), 7q36.1 (rs7781265, P=9.71 x 10(-9)), 8q24.21 (rs1948915, P=4.20 x 10(-11)), 9p21.3 (rs2811710, P=1.72 x 10(-13)), 10p12.1 (rs2790457, P=1.77 x 10(-8)), 16q23.1 (rs7193541, P=5.00 x 10(-12)) and 20q13.13 (rs6066835, P=1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development

U2 - 10.1038/ncomms12050

DO - 10.1038/ncomms12050

M3 - Journal article

SN - 2041-1723

VL - 7

SP - 12050-

JO - Nature Communications

JF - Nature Communications

ER -

Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

Abstract

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