The Liggins Institute, The University of Auckland, Auckland, 1023, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, 1010, New Zealand.
Sci Rep. 2023 Jun 19;13(1):9879. doi: 10.1038/s41598-023-36900-z.
Understanding the genetic risk and mechanisms through which SARS-CoV-2 infection outcomes and comorbidities interact to impact acute and long-term sequelae is essential if we are to reduce the ongoing health burdens of the COVID-19 pandemic. Here we use a de novo protein diffusion network analysis coupled with tissue-specific gene regulatory networks, to examine putative mechanisms for associations between SARS-CoV-2 infection outcomes and comorbidities. Our approach identifies a shared genetic aetiology and molecular mechanisms for known and previously unknown comorbidities of SARS-CoV-2 infection outcomes. Additionally, genomic variants, genes and biological pathways that provide putative causal mechanisms connecting inherited risk factors for SARS-CoV-2 infection and coronary artery disease and Parkinson's disease are identified for the first time. Our findings provide an in depth understanding of genetic impacts on traits that collectively alter an individual's predisposition to acute and post-acute SARS-CoV-2 infection outcomes. The existence of complex inter-relationships between the comorbidities we identify raises the possibility of a much greater post-acute burden arising from SARS-CoV-2 infection if this genetic predisposition is realised.
如果我们要降低 COVID-19 大流行造成的持续健康负担，了解 SARS-CoV-2 感染结果和合并症通过何种遗传风险和机制相互作用来影响急性和长期后遗症至关重要。在这里，我们使用从头开始的蛋白质扩散网络分析与组织特异性基因调控网络相结合，来检查 SARS-CoV-2 感染结果和合并症之间关联的潜在机制。我们的方法确定了 SARS-CoV-2 感染结果的已知和以前未知合并症之间的共同遗传病因和分子机制。此外，还首次确定了与 SARS-CoV-2 感染和冠状动脉疾病以及帕金森病的遗传风险因素相关的基因组变异、基因和生物途径，这些因素为提供了连接 SARS-CoV-2 感染的遗传风险因素与冠心病和帕金森病的潜在因果机制。我们的研究结果深入了解了对改变个体对 SARS-CoV-2 感染的急性和急性后感染结果易感性的特征的遗传影响。我们确定的合并症之间存在复杂的相互关系，这增加了如果这种遗传易感性得到实现，由 SARS-CoV-2 感染引起的急性后负担更大的可能性。
