文章：

SOHLH2基因的胚系变异影响多发性骨髓瘤的风险

Germline variants at SOHLH2 influence multiple myeloma risk

原文发布日期：2021-04-19

DOI: 10.1038/s41408-021-00468-6

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) is caused by the uncontrolled, clonal expansion of plasma cells. While there is epidemiological evidence for inherited susceptibility, the molecular basis remains incompletely understood. We report a genome-wide association study totalling 5,320 cases and 422,289 controls from four Nordic populations, and find a novel MM risk variant at SOHLH2 at 13q13.3 (risk allele frequency = 3.5%; odds ratio = 1.38; P = 2.2 × 10−14). This gene encodes a transcription factor involved in gametogenesis that is normally only weakly expressed in plasma cells. The association is represented by 14 variants in linkage disequilibrium. Among these, rs75712673 maps to a genomic region with open chromatin in plasma cells, and upregulates SOHLH2 in this cell type. Moreover, rs75712673 influences transcriptional activity in luciferase assays, and shows a chromatin looping interaction with the SOHLH2 promoter. Our work provides novel insight into MM susceptibility.
 

摘要翻译： 

多发性骨髓瘤（MM）是由浆细胞不受控制的克隆性增殖引起。尽管存在遗传易感性的流行病学证据，但其分子基础仍未完全阐明。我们报告了一项涵盖四个北欧人群、总计5，320例病例和422，289例对照的全基因组关联研究，并在13q13.3的SOHLH2基因位点发现了一个新的MM风险变异（风险等位基因频率=3.5%；比值比=1.38；P=2.2×10⁻¹⁴）。该基因编码一种参与配子发生的转录因子，通常在浆细胞中仅微弱表达。该关联由14个处于连锁不平衡状态的变异所代表。其中，rs75712673定位于浆细胞中具有开放染色质的基因组区域，并上调该细胞类型中SOHLH2的表达。此外，rs75712673在荧光素酶实验中影响转录活性，并显示出与SOHLH2启动子的染色质环互作。我们的研究为MM易感性提供了新的见解。

原文链接：

Germline variants at SOHLH2 influence multiple myeloma risk