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

Mitchell, Jonathan S; Li, Ni; Weinhold, Niels; Försti, Asta LU ; Ali, Mina LU ; van Duin, Mark; Thorleifsson, Gudmar; Johnson, D C; Chen, B. and Halvarsson, Britt-Marie LU , et al. (2016) In Nature Communications 7.
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,... (More)

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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Nature Communications
volume
7
publisher
Nature Publishing Group
external identifiers
  • Scopus:84977123396
ISSN
2041-1723
DOI
10.1038/ncomms12050
language
English
LU publication?
yes
id
44e94020-f867-4d82-818d-39eb100d6a67
date added to LUP
2016-08-25 09:28:21
date last changed
2016-10-28 12:12:50
@misc{44e94020-f867-4d82-818d-39eb100d6a67,
  abstract     = {<p>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.</p>},
  author       = {Mitchell, Jonathan S and Li, Ni and Weinhold, Niels and Försti, Asta and Ali, Mina and van Duin, Mark and Thorleifsson, Gudmar and Johnson, D C and Chen, B. and Halvarsson, Britt-Marie and Gudbjartsson, Daniel F and Kuiper, Rowan and Stephens, Owen W and Bertsch, Uta and Broderick, Peter and Campo, Chiara and Einsele, Hermann and Gregory, Walter A and Gullberg, Urban and Henrion, Marc and Hillengass, Jens and Hoffmann, Per and Jackson, Graham H and Johnsson, Ellinor and Jöud, Magnus and Kristinsson, Sigurður Y and Lenhoff, Stig and Lenive, Oleg and Mellqvist, Ulf-Henrik and Migliorini, Gabriele and Nahi, Hareth and Nelander, Sven and Nickel, Jolanta and Nöthen, Markus M and Rafnar, Thorunn and Ross, Fiona M and da Silva Filho, M.I. and Swaminathan, Bhairavi and Thomsen, H. and Turesson, Ingemar and Vangsted, Annette and Vogel, Ulla and Waage, Anders and Walker, Brian A and Wihlborg, Anna-Karin and Broyl, Annemiek and Davies, Faith E and Thorsteinsdottir, Unnur and Langer, Christian and Hansson, Markus and Kaiser, Martin and Sonneveld, Pieter and Stefansson, Kari and Morgan, Gareth J and Goldschmidt, Hartmut and Hemminki, Kari and Nilsson, Björn and Houlston, Richard S},
  issn         = {2041-1723},
  language     = {eng},
  publisher    = {ARRAY(0xcbbcff8)},
  series       = {Nature Communications},
  title        = {Genome-wide association study identifies multiple susceptibility loci for multiple myeloma},
  url          = {http://dx.doi.org/10.1038/ncomms12050},
  volume       = {7},
  year         = {2016},
}