文章：

多发性骨髓瘤与慢性淋巴细胞白血病之间的遗传相关性为两者共享的病因提供了证据

Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology

原文发布日期：2018-12-21

DOI: 10.1038/s41408-018-0162-8

类型: Article

开放获取: 是

英文摘要：

The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.

摘要翻译： 

不同类型的B细胞恶性肿瘤在家族中聚集的现象提示其可能存在共同的病因学基础。为验证这一假设，我们对多发性骨髓瘤（MM）和慢性淋巴细胞白血病（CLL）的全基因组关联研究（GWAS）数据集进行了跨性状连锁不平衡评分回归分析，总样本量包含11,734例患者和29,468例对照。研究显示这两种B细胞恶性肿瘤存在显著遗传相关性（Rg=0.4，P=0.0046）。进一步发现，45个已知CLL风险位点中有4个与MM风险相关，23个已知MM风险位点中有5个与CLL风险相关。通过整合eQTL、Hi-C和ChIP-seq数据，我们证实这些多效性风险位点富集于B细胞调控元件，并涉及B细胞发育相关基因。这些数据揭示了影响CLL与MM发展的共同生物学通路，深化了我们对B细胞恶性肿瘤病因学基础的理解。

原文链接：

Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology