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 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. Previous genome-wide association studies have identified loci associated with the risk of multiple myeloma. Here, the authors present a meta-analysis of six genome wide association studies of the disease and identify eight new loci; functional studies identify genes as candidates for the basis of these associations.