DNA from multiple viral species is associated with Alzheimer's disease risk
Marlene Tejeda, John Farrell, Congcong Zhu, Lee Wetzler, Kathryn L. Lunetta, William S. Bush, Eden R. Martin, Li‐San Wang, Gerard D. Schellenberg, Margaret A. Pericak‐Vance, Jonathan L. Haines, Lindsay A. Farrer, Richard Sherva- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
INTRODUCTION
Multiple infectious agents, including viruses, bacteria, fungi, and protozoa, have been linked to Alzheimer's disease (AD) risk by independent lines of evidence. We explored this association by comparing the frequencies of viral species identified in a large sample of AD cases and controls.
METHODS
DNA sequence reads that did not align to the human genome in sequences were mapped to viral reference sequences, quantified, and then were tested for association with AD in whole exome sequences (WES) and whole genome sequences (WGS) datasets.
RESULTS
Several viruses were significant predictors of AD according to the machine learning classifiers. Subsequent regression analyses showed that herpes simplex type 1 (HSV‐1) (odds ratio [OR] = 3.71, p = 8.03 × 10−4) and human papillomavirus 71 (HPV‐71; OR = 3.56, p = 0.02), were significantly associated with AD after Bonferroni correction. The phylogenetic‐related cluster of Herpesviridae was significantly associated with AD in several strata of the data (p < 0.01).
DISCUSSION
Our results support the hypothesis that viral infection, especially HSV‐1, is associated with AD risk.