全基因组关联研究鉴定出多发性骨髓瘤的多个易感位点。
Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.
机构信息
Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
出版信息
Nat Commun. 2016 Jul 1;7:12050. doi: 10.1038/ncomms12050.
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.
多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，具有显著的遗传基础。全基因组关联研究改变了我们对 MM 易感性的认识，但个别研究发现风险基因座的能力有限。在这里，我们对这些 GWAS 进行了荟萃分析，增加了一项新的 GWAS 并进行了复制分析，共涉及 9866 例病例和 239188 例对照。我们证实了所有已知的九个风险基因座，并在 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)）和 20q13.13（rs6066835，P=1.36×10(-13)）发现了八个新的风险基因座，这些基因座定位于 JARID2、ATG5、SMARCD3、CCAT1、CDKN2A、WAC、RFWD3 和 PREX1 或附近。这些发现为 MM 的多基因模型提供了额外的支持，并深入了解了肿瘤发展的生物学基础。
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