DNA from multiple viral species is associated with Alzheimer's disease risk
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...
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| Published in | Alzheimer's & dementia Vol. 20; no. 1; pp. 253 - 265 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
John Wiley & Sons, Inc
01.01.2024
John Wiley and Sons Inc |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1552-5260 1552-5279 1552-5279 |
| DOI | 10.1002/alz.13414 |
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| 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. |
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| AbstractList | 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. 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. 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. 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). Our results support the hypothesis that viral infection, especially HSV-1, is associated with AD risk. 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. 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.INTRODUCTIONMultiple 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.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.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.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).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).Our results support the hypothesis that viral infection, especially HSV-1, is associated with AD risk.DISCUSSIONOur results support the hypothesis that viral infection, especially HSV-1, is associated with AD risk. |
| Author | Wang, Li‐San Schellenberg, Gerard D. Farrell, John Zhu, Congcong Wetzler, Lee Bush, William S. Farrer, Lindsay A. Haines, Jonathan L. Pericak‐Vance, Margaret A. Tejeda, Marlene Sherva, Richard Lunetta, Kathryn L. Martin, Eden R. |
| AuthorAffiliation | 7 Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania 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 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 10 Departments of Epidemiology 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 8 Departments of Medicine Neurology and Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA 4 Depart |
| AuthorAffiliation_xml | – name: 9 Ophthalmology Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA – name: 8 Departments of Medicine Neurology and Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA – name: 4 Departments of Biostatistics Boston University School of Public Health Boston Massachusetts USA – name: 10 Departments of Epidemiology Boston University School of Public Health Boston Massachusetts USA – name: 7 Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA – name: 5 Department of Population & Quantitative Health Sciences Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine Cleveland Ohio USA – name: 1 Departments of Medicine Biomedical Genetics Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA – name: 3 Departments of Medicine Microbiology Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA – name: 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 – name: 2 Departments of Medicine Infectious Disease Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA |
| Author_xml | – sequence: 1 givenname: Marlene surname: Tejeda fullname: Tejeda, Marlene organization: Boston University Chobanian & Avedisian School of Medicine – sequence: 2 givenname: John surname: Farrell fullname: Farrell, John organization: Boston University Chobanian & Avedisian School of Medicine – sequence: 3 givenname: Congcong surname: Zhu fullname: Zhu, Congcong organization: Boston University Chobanian & Avedisian School of Medicine – sequence: 4 givenname: Lee surname: Wetzler fullname: Wetzler, Lee organization: Boston University Chobanian & Avedisian School of Medicine – sequence: 5 givenname: Kathryn L. surname: Lunetta fullname: Lunetta, Kathryn L. organization: Boston University School of Public Health – sequence: 6 givenname: William S. surname: Bush fullname: Bush, William S. organization: Case Western Reserve University School of Medicine – sequence: 7 givenname: Eden R. surname: Martin fullname: Martin, Eden R. organization: University of Miami – sequence: 8 givenname: Li‐San surname: Wang fullname: Wang, Li‐San organization: University of Pennsylvania Perelman School of Medicine – sequence: 9 givenname: Gerard D. surname: Schellenberg fullname: Schellenberg, Gerard D. organization: University of Pennsylvania Perelman School of Medicine – sequence: 10 givenname: Margaret A. surname: Pericak‐Vance fullname: Pericak‐Vance, Margaret A. organization: University of Miami – sequence: 11 givenname: Jonathan L. surname: Haines fullname: Haines, Jonathan L. organization: Case Western Reserve University School of Medicine – sequence: 12 givenname: Lindsay A. surname: Farrer fullname: Farrer, Lindsay A. organization: Boston University School of Public Health – sequence: 13 givenname: Richard surname: Sherva fullname: Sherva, Richard email: sherva@bu.edu organization: Boston University Chobanian & Avedisian School of Medicine |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37578203$$D View this record in MEDLINE/PubMed |
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| Keywords | whole genome sequencing antiviral agents human papillomavirus Alzheimer's disease sequencing project torque teno viruses Alzheimer's disease whole exome sequencing herpes simplex |
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Multiple infectious agents, including viruses, bacteria, fungi, and protozoa, have been linked to Alzheimer's disease (AD) risk by independent... Multiple infectious agents, including viruses, bacteria, fungi, and protozoa, have been linked to Alzheimer's disease (AD) risk by independent lines of... INTRODUCTION Multiple infectious agents, including viruses, bacteria, fungi, and protozoa, have been linked to Alzheimer's disease (AD) risk by independent... |
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| SubjectTerms | 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 |
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| Title | DNA from multiple viral species is associated with Alzheimer's disease risk |
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