当前位置: X-MOL 学术medRxiv. Genet. Genom. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The genetic architecture of human infectious diseases and pathogen-induced cellular phenotypes
medRxiv - Genetic and Genomic Medicine Pub Date : 2021-02-13 , DOI: 10.1101/2020.07.19.20157404
Andrew T. Hale , Dan Zhou , Rebecca L. Sale , Lisa Bastarache , Liuyang Wang , Sandra S. Zinkel , Steven J. Schiff , Dennis C. Ko , Eric R. Gamazon

Here, we develop a genetics-anchored framework to decipher mechanisms of infectious disease (ID) risk and infer causal effect on potential complications. We perform transcriptome-wide association studies (TWAS) of 35 ID traits in 27,615 individuals in a broad collection of human tissues, identifying 70 gene-level associations with 26 ID traits, with replication in two large-scale biobanks. A phenome-scale scan and Mendelian Randomization of the 70 gene-level associations across 197 traits proposes a molecular basis for known complications of the ID traits. This rich resource of host genetic associations with pathogen cultures and 16S-rRNA-based microbiome variation provides a platform to investigate host-pathogen interactions. To identify relevant cellular processes, we develop a TWAS repository of 79 pathogen-exposure induced cellular phenotypes. Our study will facilitate mechanistic insights into the role of host genetic variation on ID risk and pathophysiology, with important implications for our molecular understanding of severe phenotypic outcomes.

中文翻译:

人类传染病的遗传结构和病原体诱导的细胞表型

在这里,我们建立了遗传锚定的框架,以破译传染病(ID)风险的机制,并推断潜在并发症的因果关系。我们在人类组织的广泛集合中对27,615个个体中的35个ID特性进行了转录组范围的关联研究(TWAS),确定了具有26个ID特性的70个基因水平关联,并在两个大型生物库中进行了复制。一项对197个性状的70个基因水平关联的表型规模扫描和孟德尔随机化,为ID性状已知并发症提供了分子基础。与病原体培养和基于16S-rRNA的微生物组变异相关的宿主遗传关联的丰富资源提供了研究宿主与病原体相互作用的平台。为了确定相关的细胞过程,我们开发了79种病原体暴露诱导的细胞表型的TWAS信息库。
更新日期:2021-02-15
down
wechat
bug