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

Jonathan S Mitchell; Ni Li; Niels Weinhold; Asta Försti; Mina Ali; Mark van Duin; Gudmar Thorleifsson; David C Johnson; Bowang Chen; Britt-Marie Halvarsson; Daniel F Gudbjartsson; Rowan Kuiper; Owen W Stephens; Uta Bertsch; Peter Broderick; Chiara Campo; Hermann Einsele; Walter A Gregory; Urban Gullberg; Marc Henrion; Jens Hillengass; Per Hoffmann; Graham H Jackson; Ellinor Johnsson; Magnus Jöud; Sigurður Y Kristinsson; Stig Lenhoff; Oleg Lenive; Ulf-Henrik Mellqvist; Gabriele Migliorini; Hareth Nahi; Sven Nelander; Jolanta Nickel; Markus M Nöthen; Thorunn Rafnar; Fiona M Ross; Miguel Inacio da Silva Filho; Bhairavi Swaminathan; Hauke Thomsen; Ingemar Turesson; Annette Vangsted; Ulla Vogel; Anders Waage; Brian A Walker; Anna-Karin Wihlborg; Annemiek Broyl; Faith E Davies; Unnur Thorsteinsdottir; Christian Langer; Markus Hansson; Martin Kaiser; Pieter Sonneveld; Kari Stefansson; Gareth J Morgan; Hartmut Goldschmidt; Kari Hemminki; Björn Nilsson; Richard S Houlston

doi:10.1038/ncomms12050

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

Jonathan S Mitchell, Ni Li, Niels Weinhold, Asta Försti, Mina Ali, Mark van Duin, Gudmar Thorleifsson, David C Johnson, Bowang Chen, Britt-Marie Halvarsson, Daniel F Gudbjartsson, Rowan Kuiper, Owen W Stephens, Uta Bertsch, Peter Broderick, Chiara Campo, Hermann Einsele, Walter A Gregory, Urban Gullberg, Marc HenrionJens Hillengass, Per Hoffmann, Graham H Jackson, Ellinor Johnsson, Magnus Jöud, Sigurður Y Kristinsson, Stig Lenhoff, Oleg Lenive, Ulf-Henrik Mellqvist, Gabriele Migliorini, Hareth Nahi, Sven Nelander, Jolanta Nickel, Markus M Nöthen, Thorunn Rafnar, Fiona M Ross, Miguel Inacio da Silva Filho, Bhairavi Swaminathan, Hauke Thomsen, Ingemar Turesson, Annette Vangsted, Ulla Vogel, Anders Waage, Brian A Walker, Anna-Karin Wihlborg, Annemiek Broyl, Faith E Davies, Unnur Thorsteinsdottir, Christian Langer, Markus Hansson, Martin Kaiser, Pieter Sonneveld, Kari Stefansson, Gareth J Morgan, Hartmut Goldschmidt, Kari Hemminki, Björn Nilsson, Richard S Houlston

Department of Clinical Medicine

79 Citations (Scopus)

Abstract

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 × 10(-8)), 6q21 (rs9372120, P=9.09 × 10(-15)), 7q36.1 (rs7781265, P=9.71 × 10(-9)), 8q24.21 (rs1948915, P=4.20 × 10(-11)), 9p21.3 (rs2811710, P=1.72 × 10(-13)), 10p12.1 (rs2790457, P=1.77 × 10(-8)), 16q23.1 (rs7193541, P=5.00 × 10(-12)) and 20q13.13 (rs6066835, P=1.36 × 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
Article number	12050
Journal	Nature Communications
Volume	7
Number of pages	9
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms12050
Publication status	Published - 1 Jul 2016

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Mitchell, J. S., Li, N., Weinhold, N., Försti, A., Ali, M., van Duin, 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, Article 12050. https://doi.org/10.1038/ncomms12050

Mitchell, JS, Li, N, Weinhold, N, Försti, A, Ali, M, van Duin, M, Thorleifsson, G, Johnson, DC, Chen, B, Halvarsson, B-M, 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, Jöud, M, Kristinsson, SY, Lenhoff, S, Lenive, O, Mellqvist, U-H, Migliorini, G, Nahi, H, Nelander, S, Nickel, J, Nöthen, MM, Rafnar, T, Ross, FM, da Silva Filho, MI, Swaminathan, B, Thomsen, H, Turesson, I, Vangsted, A, Vogel, U, Waage, A, Walker, BA, Wihlborg, A-K, 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, 12050. https://doi.org/10.1038/ncomms12050

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abstract = "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 × 10(-8)), 6q21 (rs9372120, P=9.09 × 10(-15)), 7q36.1 (rs7781265, P=9.71 × 10(-9)), 8q24.21 (rs1948915, P=4.20 × 10(-11)), 9p21.3 (rs2811710, P=1.72 × 10(-13)), 10p12.1 (rs2790457, P=1.77 × 10(-8)), 16q23.1 (rs7193541, P=5.00 × 10(-12)) and 20q13.13 (rs6066835, P=1.36 × 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.",

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author = "Mitchell, {Jonathan S} and Ni Li and Niels Weinhold and Asta F{\"o}rsti and Mina Ali and {van Duin}, Mark and Gudmar Thorleifsson and Johnson, {David C} and Bowang Chen and Britt-Marie Halvarsson and Gudbjartsson, {Daniel F} and Rowan Kuiper and Stephens, {Owen W} and Uta Bertsch and Peter Broderick and Chiara Campo and Hermann Einsele and Gregory, {Walter A} and Urban Gullberg and Marc Henrion and Jens Hillengass and Per Hoffmann and Jackson, {Graham H} and Ellinor Johnsson and Magnus J{\"o}ud and Kristinsson, {Sigur{\dh}ur Y} and Stig Lenhoff and Oleg Lenive and Ulf-Henrik Mellqvist and Gabriele Migliorini and Hareth Nahi and Sven Nelander and Jolanta Nickel and N{\"o}then, {Markus M} and Thorunn Rafnar and Ross, {Fiona M} and {da Silva Filho}, {Miguel Inacio} and Bhairavi Swaminathan and Hauke Thomsen and Ingemar Turesson and Annette Vangsted and Ulla Vogel and Anders Waage and Walker, {Brian A} and Anna-Karin Wihlborg and Annemiek Broyl and Davies, {Faith E} and Unnur Thorsteinsdottir and Christian Langer and Markus Hansson and Martin Kaiser and Pieter Sonneveld and Kari Stefansson and Morgan, {Gareth J} and Hartmut Goldschmidt and Kari Hemminki and Bj{\"o}rn Nilsson and Houlston, {Richard S}",

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

AU - Mitchell, Jonathan S

AU - Li, Ni

AU - Weinhold, Niels

AU - Försti, Asta

AU - Ali, Mina

AU - van Duin, Mark

AU - Thorleifsson, Gudmar

AU - Johnson, David C

AU - Chen, Bowang

AU - Halvarsson, Britt-Marie

AU - Gudbjartsson, Daniel F

AU - Kuiper, Rowan

AU - Stephens, Owen W

AU - Bertsch, Uta

AU - Broderick, Peter

AU - Campo, Chiara

AU - Einsele, Hermann

AU - Gregory, Walter A

AU - Gullberg, Urban

AU - Henrion, Marc

AU - Hillengass, Jens

AU - Hoffmann, Per

AU - Jackson, Graham H

AU - Johnsson, Ellinor

AU - Jöud, Magnus

AU - Kristinsson, Sigurður Y

AU - Lenhoff, Stig

AU - Lenive, Oleg

AU - Mellqvist, Ulf-Henrik

AU - Migliorini, Gabriele

AU - Nahi, Hareth

AU - Nelander, Sven

AU - Nickel, Jolanta

AU - Nöthen, Markus M

AU - Rafnar, Thorunn

AU - Ross, Fiona M

AU - da Silva Filho, Miguel Inacio

AU - Swaminathan, Bhairavi

AU - Thomsen, Hauke

AU - Turesson, Ingemar

AU - Vangsted, Annette

AU - Vogel, Ulla

AU - Waage, Anders

AU - Walker, Brian A

AU - Wihlborg, Anna-Karin

AU - Broyl, Annemiek

AU - Davies, Faith E

AU - Thorsteinsdottir, Unnur

AU - Langer, Christian

AU - Hansson, Markus

AU - Kaiser, Martin

AU - Sonneveld, Pieter

AU - Stefansson, Kari

AU - Morgan, Gareth J

AU - Goldschmidt, Hartmut

AU - Hemminki, Kari

AU - Nilsson, Björn

AU - Houlston, Richard S

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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 × 10(-8)), 6q21 (rs9372120, P=9.09 × 10(-15)), 7q36.1 (rs7781265, P=9.71 × 10(-9)), 8q24.21 (rs1948915, P=4.20 × 10(-11)), 9p21.3 (rs2811710, P=1.72 × 10(-13)), 10p12.1 (rs2790457, P=1.77 × 10(-8)), 16q23.1 (rs7193541, P=5.00 × 10(-12)) and 20q13.13 (rs6066835, P=1.36 × 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 - 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 × 10(-8)), 6q21 (rs9372120, P=9.09 × 10(-15)), 7q36.1 (rs7781265, P=9.71 × 10(-9)), 8q24.21 (rs1948915, P=4.20 × 10(-11)), 9p21.3 (rs2811710, P=1.72 × 10(-13)), 10p12.1 (rs2790457, P=1.77 × 10(-8)), 16q23.1 (rs7193541, P=5.00 × 10(-12)) and 20q13.13 (rs6066835, P=1.36 × 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.

KW - Journal Article

U2 - 10.1038/ncomms12050

DO - 10.1038/ncomms12050

M3 - Journal article

C2 - 27363682

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 12050

ER -

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

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