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

Nat Commun. 2016 Jul 1:7:12050. doi: 10.1038/ncomms12050.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Autophagy-Related Protein 5 / genetics
  • Case-Control Studies
  • Chromosomal Proteins, Non-Histone
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Multiple Myeloma / genetics*
  • Polycomb Repressive Complex 2 / genetics
  • RNA, Long Noncoding / genetics
  • Transcription Factors / genetics
  • Ubiquitin-Protein Ligases / genetics

Substances

  • ATG5 protein, human
  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Protein 5
  • CCAT1 long noncoding RNA, human
  • CDKN2A protein, human
  • Chromosomal Proteins, Non-Histone
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • Guanine Nucleotide Exchange Factors
  • JARID2 protein, human
  • PREX1 protein, human
  • RNA, Long Noncoding
  • SMARCD3 protein, human
  • Transcription Factors
  • WAC protein, human
  • Polycomb Repressive Complex 2
  • RFWD3 protein, human
  • Ubiquitin-Protein Ligases