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

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  • 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
  • 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

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 languageEnglish
Article number12050
JournalNature Communications
Volume7
Number of pages9
ISSN2041-1723
DOIs
Publication statusPublished - 2016

    Research areas

  • Journal Article

ID: 177067103