DNA from multiple viral species is associated with Alzheimer's disease risk

• Published in: Alzheimer's & dementia Vol. 20; no. 1; pp. 253 - 265
• Main Authors: Tejeda, Marlene, Farrell, John, Zhu, Congcong, Wetzler, Lee, Lunetta, Kathryn L., Bush, William S., Martin, Eden R., Wang, Li‐San, Schellenberg, Gerard D., Pericak‐Vance, Margaret A., Haines, Jonathan L., Farrer, Lindsay A., Sherva, Richard
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2024; John Wiley and Sons Inc
• Subjects: Alzheimer Disease - complications; Alzheimer's disease; Alzheimer's disease sequencing project; antiviral agents; Bacteria; Deoxyribonucleic acid; DNA; Genomics; Herpes Simplex; Herpes viruses; Herpesvirus 1, Human - genetics; Human papillomavirus; Humans; Pathology; Phylogeny; Sequences; torque teno viruses; Viral infections; whole exome sequencing; whole genome sequencing; whole genome sequencing; antiviral agents; human papillomavirus; Alzheimer's disease sequencing project; torque teno viruses; Alzheimer's disease; whole exome sequencing; herpes simplex
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.13414

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.