The landscape of host genetic factors involved in immune response to common viral infections.
The landscape of host genetic factors involved in immune response to common viral infections.
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DOI：
10.1101/2020.05.01.20088054
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发表时间：
2020-10-27
期刊：
影响因子：
12.3
通讯作者：
Witte, John S
中科院分区：
文献类型：
--
作者：
Kachuri, Linda;Francis, Stephen S;Witte, John S
人类和病毒已经共同进化了数千年，导致了复杂的宿主遗传结构。了解对病毒感染的免疫应答的遗传机制提供了对疾病病因学和治疗机会的深入了解。方法：我们进行了一项全面的研究，包括全基因组和全转录组关联分析，以确定与免疫球蛋白G抗体对16种病毒的28种抗原的应答相关的遗传位点，使用来自英国生物库队列的7924名欧洲血统参与者的血清学数据。结果：人类白细胞抗原（HLA）II类区域的信号占主导地位的病毒抗体反应的景观，有40个独立的位点和14个独立的经典等位基因，其中7个表现出多效性的病毒家族。我们鉴定了与血清反应性相关的特定氨基酸（AA）残基，最强的关联存在于EB病毒（EBV）、水痘带状疱疹病毒（VZV）、人类疱疹病毒7型（HHV 7）和默克尔细胞多瘤病毒（MCV）DR β 1内第11、13、71和74位的一系列AA位置中。全基因组关联分析发现7个HLA以外的新基因位点与病毒抗体应答相关（P
INTRODUCTION: Humans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the genetic mechanisms of immune response to viral infection provides insight into disease etiology and therapeutic opportunities.METHODS: We conducted a comprehensive study including genome-wide and transcriptome-wide association analyses to identify genetic loci associated with immunoglobulin G antibody response to 28 antigens for 16 viruses using serological data from 7924 European ancestry participants in the UK Biobank cohort.RESULTS: Signals in human leukocyte antigen (HLA) class II region dominated the landscape of viral antibody response, with 40 independent loci and 14 independent classical alleles, 7 of which exhibited pleiotropic effects across viral families. We identified specific amino acid (AA) residues that are associated with seroreactivity, the strongest associations presented in a range of AA positions within DRbeta1 at positions 11, 13, 71, and 74 for Epstein-Barr Virus (EBV), Varicella Zoster Virus (VZV), Human Herpes virus 7, (HHV7) and Merkel cell polyomavirus (MCV). Genome-wide association analyses discovered 7 novel genetic loci outside the HLA associated with viral antibody response (P