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

Author:

Tejeda Marlene1,Farrell John1,Zhu Congcong1,Wetzler Lee23,Lunetta Kathryn L.4,Bush William S.5,Martin Eden R.6,Wang Li‐San7,Schellenberg Gerard D.7,Pericak‐Vance Margaret A.6,Haines Jonathan L.5,Farrer Lindsay A.148910,Sherva Richard1

Affiliation:

1. Departments of Medicine Biomedical Genetics Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA

2. Departments of Medicine Infectious Disease Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA

3. Departments of Medicine Microbiology Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA

4. Departments of Biostatistics Boston University School of Public Health Boston Massachusetts USA

5. Department of Population & Quantitative Health Sciences Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine Cleveland Ohio USA

6. John P. Hussman Institute for Human Genomics and Dr John T. MacDonald Foundation Department of Human Genetics Miller School of Medicine University of Miami Miami Florida USA

7. Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

8. Departments of Medicine Neurology and Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA

9. Ophthalmology Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA

10. Departments of Epidemiology Boston University School of Public Health Boston Massachusetts USA

Abstract

AbstractINTRODUCTIONMultiple 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.METHODSDNA 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.RESULTSSeveral 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).DISCUSSIONOur results support the hypothesis that viral infection, especially HSV‐1, is associated with AD risk.

Funder

National Heart, Lung, and Blood Institute

National Institute on Aging

National Institutes of Health

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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