Chen Jingchun, Cammann Davis, Liu Tingwei, Liu Yimei, Cummings Melika, Chen Xiangning, Oh Edwin, Rotter Jerome
University of Nevada Las Vegas.
The university of Texas Health Science Center at Houston.
Res Sq. 2024 Dec 24:rs.3.rs-5619229. doi: 10.21203/rs.3.rs-5619229/v1.
The global outbreak of COVID-19, caused by the SARS-CoV-2 virus, has been linked to long-term neurological complications, including an increased risk of Alzheimer's disease (AD) among older adults. However, the precise genetic impact of COVID-19 on long-term AD development remains unclear. This study leveraged genome-wide association study (GWAS) data and genotype data to explore the genetic association between AD and various COVID-19 phenotypes across European ancestry (EA) and African ancestry (AA) cohorts, and the possibility of a causal effect of COVID-19 on AD. We first calculated polygenic risk scores (PRSs) of three COVID-19 phenotypes in AD cases and controls from both EA and AA populations, then determined the genetic associations between COVID-19 PRSs and AD by logistic regression analyses with or without adjusting for age, sex, and genotypes. Significant positive associations were found between AD diagnosis and COVID-19 PRSs in both populations, with the strongest associations identified in the AA population. However, Mendelian randomization (MR) analyses revealed no evidence of a causal effect of COVID-19 phenotypes on AD liability. We explored this finding further through the analysis of shared genomic regions between the COVID-19 phenotypes and AD and found a region of overlap on chromosome 17 that was highly pleiotropic for traits implicating immune function, psychiatric disorders, and lung function phenotypes. These findings suggest that while COVID-19 and AD share overlapping polygenic contributions involving peripheral genes across multiple traits, they lack a direct connection involving core genes that drive the development of their respective pathologies.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒引起的新型冠状病毒肺炎（COVID-19）全球大流行与长期神经并发症有关，包括老年人患阿尔茨海默病（AD）的风险增加。然而，COVID-19对AD长期发展的确切遗传影响仍不清楚。本研究利用全基因组关联研究（GWAS）数据和基因型数据，探讨欧洲血统（EA）和非洲血统（AA）队列中AD与各种COVID-19表型之间的遗传关联，以及COVID-19对AD的因果效应可能性。我们首先计算了来自EA和AA人群的AD病例和对照中三种COVID-19表型的多基因风险评分（PRS），然后通过逻辑回归分析确定COVID-19 PRS与AD之间的遗传关联，分析时调整或不调整年龄、性别和基因型。在两个人群中均发现AD诊断与COVID-19 PRS之间存在显著正相关，在AA人群中相关性最强。然而，孟德尔随机化（MR）分析未发现COVID-19表型对AD易感性有因果效应的证据。我们通过分析COVID-19表型与AD之间的共享基因组区域进一步探究了这一发现，发现在17号染色体上有一个重叠区域，该区域对涉及免疫功能、精神障碍和肺功能表型的性状具有高度多效性。这些发现表明，虽然COVID-19和AD在涉及多个性状的外周基因方面有重叠的多基因贡献，但它们缺乏涉及驱动各自病理发展的核心基因的直接联系。
