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

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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Item Type:	Article
Authors/Creators:	Mitchell, JS Li, N Weinhold, N Försti, A Ali, M Van Duin, M Thorleifsson, G Johnson, DC Chen, B Halvarsson, BM Gudbjartsson, DF Kuiper, R Stephens, OW Bertsch, U Broderick, P Campo, C Einsele, H Gregory, WA https://orcid.org/0000-0003-2641-8416 Gullberg, U Henrion, M Hillengass, J Hoffmann, P Jackson, GH Johnsson, E Jöud, M Kristinsson, SY Lenhoff, S Lenive, O Mellqvist, UH 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, 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
Copyright, Publisher and Additional Information:	© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Dates:	Accepted: 24 May 2016 Published (online): 1 July 2016 Published: 1 July 2016
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Clinical Trials Research (LICTR) (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	07 Dec 2016 11:20
Last Modified:	05 Oct 2017 16:24
Published Version:	https://doi.org/10.1038/ncomms12050
Status:	Published
Publisher:	Nature Publishing Group
Identification Number:	10.1038/ncomms12050
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:108879

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

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