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

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...

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Main Authors: Mitchell, Jonathan S. (Author) , Weinhold, Niels (Author) , Bertsch, Uta (Author) , Hillengaß, Jens (Author) , Nickel, Jolanta (Author) , Goldschmidt, Hartmut (Author)
Format: Article (Journal)
Language:English
Published: 1 Jul 2016
In: Nature Communications
Year: 2016, Volume: 7, Pages: 1-9
ISSN:2041-1723
DOI:10.1038/ncomms12050
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/ncomms12050
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/ncomms12050
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Author Notes: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 and Richard S. Houlston

MARC

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520 |a 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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