Shared Genetic Architecture Between COVID-19 Severity and Alzheimer's Disease Across European and African Ancestries

Shared Genetic Architecture Between COVID-19 Severity and Alzheimer's Disease Across European and African Ancestries | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 30 January 2025 V1 Latest version Share on Shared Genetic Architecture Between COVID-19 Severity and Alzheimer's Disease Across European and African Ancestries Authors : Jingchun Chen [email protected] , Davis Cammann 0009-0008-2202-5790 , Tingwei Liu , Yimei Lu , Melika J. Cummings , Xiangning Chen , Edwin C. Oh , and Jerome Rotter Authors Info & Affiliations https://doi.org/10.22541/au.173821242.28856771/v1 258 views 116 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract The global outbreak of COVID-19 is linked to long-term neurological complications, including an increased risk of Alzheimer’s disease (AD) among older adults. We investigated whether phenotypes of COVID-19 and AD held pathological connections by analyzing the genetic relationship between them. This study explored the association between AD and polygenic risk scores (PRS) of three COVID-19 phenotypes in European ancestry (EA) and African ancestry (AA) cohorts. PRS-AD associations were determined using logistic regression models adjusted for age, sex, and APOE genotypes. Mendelian randomization (MR) was used to test putative causal relationships between the COVID-19 phenotypes and AD. We also identified overlapping genomic regions between AD and COVID-19 GWASs, and performed a phenome-wide association scan (PheWAS) in the region to identify traits associated with the shared genetic variants. Significant positive associations ( p< 0.0167) were found between COVID-19 PRSs and AD in both populations, with the strongest identified in the AA population. However, MR analyses revealed no evidence of a causal effect of COVID-19 phenotypes on AD liability in either ancestry. Exploring this finding further, we identified overlapping genetic associations on chromosome 17 between COVID-19 hospitalization, critical illness, and AD in the EA population. A PheWAS of the rs12373123 and rs199515 SNPs found within the overlapping region revealed multiple significant trait associations ( p <1.05 x10 -5 ) implicating immune function, psychiatric disorders, and lung function phenotypes. This suggests that while COVID-19 and AD share overlapping polygenic contributions found across multiple traits, they lack a direct connection involving core genes that drive the development of their respective pathologies. Supplementary Material File (ms_jmedvirol.docx) Download 154.81 KB File (tables1-3.xlsx) Download 24.16 KB Information & Authors Information Version history V1 Version 1 30 January 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords biostatistics & bioinformatics coronavirus epidemiology evolution genetic networks genetic variability genetic variation genetics sars coronavirus virus classification Authors Affiliations Jingchun Chen [email protected] University of Nevada Las Vegas View all articles by this author Davis Cammann 0009-0008-2202-5790 University of Nevada Las Vegas View all articles by this author Tingwei Liu University of Nevada Las Vegas View all articles by this author Yimei Lu University of Nevada Las Vegas View all articles by this author Melika J. Cummings University of Nevada Las Vegas View all articles by this author Xiangning Chen The University of Texas Health Science Center at Houston School of Biomedical Informatics View all articles by this author Edwin C. Oh University of Nevada Las Vegas College of Sciences View all articles by this author Jerome Rotter The Lundquist Institute View all articles by this author Metrics & Citations Metrics Article Usage 258 views 116 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Jingchun Chen, Davis Cammann, Tingwei Liu, et al. Shared Genetic Architecture Between COVID-19 Severity and Alzheimer's Disease Across European and African Ancestries. Authorea . 30 January 2025. DOI: https://doi.org/10.22541/au.173821242.28856771/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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