Year: 2019
Type: article
Study design: Observational Study
Abstract: Recent reports provide compelling evidence suggesting that common infections, including herpesviruses, play a role in Alzheimer's disease (AD) pathogenesis. However, epidemiologic literature on this topic is lacking, in part due to 1) no large datasets that include both infection history/biomarkers and AD outcomes, and 2) issues of reverse causality bias whereby AD patients are potentially more vulnerable to infections. Well-designed studies that integrate genetic epidemiology tools and methods can help overcome these issues because germline variants for infection susceptibility are determined at birth and do not change over time, thereby serving as proxies for infection exposure in the analysis of AD risk. Using previously published genome-wide association study (GWAS) risk loci for susceptibility to Epstein-Barr virus infection (a herpesvirus causing mononucleosis), we assessed whether genetic susceptibility to infections is associated with AD using summary statistics from the International Genomics of Alzheimer's Project GWAS (17,008 cases, 37,154 controls). In addition, we assessed whether genetic susceptibility to herpesvirus infections is associated with a proxy AD phenotype, i.e. whether a participant reported a biological mother or father with a diagnosis of AD/dementia in 488,377 participants with genotyping data in the UK Biobank (UKB), based on logistic regression adjusted for 12 principal components to account for population stratification. Four genetic variants previously associated with blood antigen levels of Epstein Barr virus or mononucleosis infection were associated with AD (Table 1; P<=5.9x10 for all). The direction of association was consistently positive, i.e. genetic variation associated with greater susceptibility to Epstein-Barr virus corresponds to greater risk for AD. Associations are also observed among UKB individuals whose parents were diagnosed with AD/dementia, although results were less consistent among fathers.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980748125