Human polyomaviruses are widespread in humans and can cause severe disease in immunocompromised individuals. To identify human genetic determinants of the humoral immune response against polyomaviruses, we performed genome-wide association studies and meta-analyses of qualitative and quantitative immunoglobulin G responses against BK polyomavirus (BKPyV), JC polyomavirus (JCPyV), Merkel cellpolyomavirus (MCPyV), WU polyomavirus (WUPyV), and human polyomavirus 6 (HPyV6) in 15,660 individuals of European ancestry from three independent studies. We observed significant associations for all tested viruses: JCPyV, HPyV6, and MCPyV associated with human leukocyte antigen class II variation, BKPyV and JCPyV with variants in FUT2, responsible for secretor status, MCPyV with variants in STING1, involved in interferon induction, and WUPyV with a functional variant in MUC1, previously associated with risk for gastric cancer. These results provide insights into the genetic control of a family of very prevalent human viruses, highlighting genes and pathways that play a modulating role in human humoral immunity.

中文翻译：

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针对多瘤病毒的体液免疫反应的人类基因组学

人类多瘤病毒在人类中广泛存在，可在免疫功能低下的个体中引起严重的疾病。为了确定针对多瘤病毒的体液免疫反应的人类遗传决定因素，我们对针对 BK 多瘤病毒 (BKPyV)、JC 多瘤病毒 (JCPyV)、默克尔细胞多瘤病毒 (MCPyV)、 WU 多瘤病毒 (WUPyV) 和人类多瘤病毒 6 (HPyV6) 来自三项独立研究的 15,660 名欧洲血统个体。我们观察到所有测试病毒的显着关联：JCPyV、HPyV6 和 MCPyV 与人类白细胞抗原 II 类变异相关，BKPyV 和 JCPyV 与 FUT2 变异相关，负责分泌状态，MCPyV 与 STING1 变异相关，参与干扰素诱导，和 WUPyV 在 MUC1 中具有功能变异，以前与胃癌风险相关。这些结果提供了对一个非常普遍的人类病毒家族的遗传控制的见解，突出了在人类体液免疫中发挥调节作用的基因和途径。