全基因组关联研究揭示经典霍奇金淋巴瘤的疾病易感性关键调控因子。
Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.
机构信息
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, 69120, Germany.
出版信息
Nat Commun. 2017 Dec 1;8(1):1892. doi: 10.1038/s41467-017-00320-1.
Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10), 6q23.3 (rs6928977, P = 4.62 × 10), 10p14 (rs3781093, P = 9.49 × 10), 13q34 (rs112998813, P = 4.58 × 10) and 16p13.13 (rs34972832, P = 2.12 × 10). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.
已经报道了几个经典霍奇金淋巴瘤的易感基因座。然而，大部分遗传风险仍然未知。在此，我们对两项已有的全基因组关联研究、一项新的全基因组关联研究以及总共 5314 例病例和 16749 例对照的复制进行了荟萃分析。我们确定了所有经典霍奇金淋巴瘤的风险基因座位于 6q22.33（rs9482849，P=1.52×10）和结节性硬化型霍奇金淋巴瘤的 3q28（rs4459895，P=9.43×10）、6q23.3（rs6928977，P=4.62×10）、10p14（rs3781093，P=9.49×10）、13q34（rs112998813，P=4.58×10）和 16p13.13（rs34972832，P=2.12×10）。此外，在 HLA 区域内还观察到结节性硬化型霍奇金淋巴瘤（rs9269081，HLA-DPB1*03:01，HLA-DRB1 中的 Val86）和混合细胞型霍奇金淋巴瘤（rs1633096，rs13196329，HLA-DRB1 中的 Val86）的独立基因座。新发现和已确立的风险基因座定位于活性染色质区域，并且转录因子结合的决定因素在 B 细胞发育和免疫反应中表现出过度表达。
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