DNA from multiple viral species are associated with Alzheimer’s disease risk

Details

• Alternative Title:
  Alzheimers Dement
• Personal Author:
  Tejeda, Marlene ; Farrell, John ; Zhu, Congcong ; Wetzler, Lee ; Lunetta, Kathryn L. ; Bush, William S. ; Martin, Eden R. ; Wang, Li-San ; Schellenberg, Gerard ; Pericak-Vance, Margaret A. ; Haines, Jonathan L. ; Farrer, Lindsay A. ; Sherva, Richard
• Description:
  INTRODUCTION:
  
  Multiple infectious agents, including viruses, bacteria, fungi, and protozoa, have been linked to Alzheimer 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 HSV-1 (OR=3.71, P=8.03×10−4) and 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.
  
  
• Subjects:
  Alzheimer Disease DNA Herpes Simplex Herpesvirus 1, Human Humans Phylogeny
• Keywords:
  Alzheimer’s Disease Alzheimer’s Disease Sequencing Project Antiviral Agents Herpes Simplex Human Papillomavirus Torque Teno Viruses Whole Exome Sequencing Whole Genome Sequencing
• Source:
  Alzheimers Dement. 20(1):253-265
• Pubmed ID:
  37578203
• Pubmed Central ID:
  PMC10840621
• Document Type:
  Journal Article
• Funding:
  HHSN268201100012C/HL/NHLBI NIH HHSUnited States/ ; P20 AG068082/AG/NIA NIH HHSUnited States/ ; P30 AG072975/AG/NIA NIH HHSUnited States/ ; R01 AG042188/AG/NIA NIH HHSUnited States/ ; P30 AG066444/AG/NIA NIH HHSUnited States/ ; RC2 HL102419/HL/NHLBI NIH HHSUnited States/ ; HHSN268201100009I/HL/NHLBI NIH HHSUnited States/ ; R01 AG018016/AG/NIA NIH HHSUnited States/ ; R01 AG060747/AG/NIA NIH HHSUnited States/ ; P30 AG066507/AG/NIA NIH HHSUnited States/ ; P30 AG072946/AG/NIA NIH HHSUnited States/ ; U01 AG058654/AG/NIA NIH HHSUnited States/ ; U01 HL096812/HL/NHLBI NIH HHSUnited States/ ; U54 AG052427/AG/NIA NIH HHSUnited States/ ; R01 NS017950/NS/NINDS NIH HHSUnited States/ ; P30 AG066518/AG/NIA NIH HHSUnited States/ ; R01 AG054076/AG/NIA NIH HHSUnited States/ ; R01 AG046949/AG/NIA NIH HHSUnited States/ ; R01 AG042210/AG/NIA NIH HHSUnited States/ ; U54 HG003067/HG/NHGRI NIH HHSUnited States/ ; R01 AG048927/NH/NIH HHSUnited States/ ; R01 AG057909/AG/NIA NIH HHSUnited States/ ; HHSN268201100010C/HL/NHLBI NIH HHSUnited States/ ; P20 AG068053/AG/NIA NIH HHSUnited States/ ; R01 AG009029/AG/NIA NIH HHSUnited States/ ; R01 NS069719/NS/NINDS NIH HHSUnited States/ ; R01 AG015928/AG/NIA NIH HHSUnited States/ ; P01 NS026630/NS/NINDS NIH HHSUnited States/ ; P30 AG010133/AG/NIA NIH HHSUnited States/ ; U24 AG021886/AG/NIA NIH HHSUnited States/ ; R01 AG009956/AG/NIA NIH HHSUnited States/ ; HHSN268201100008C/HL/NHLBI NIH HHSUnited States/ ; U01 HL080295/HL/NHLBI NIH HHSUnited States/ ; HHSN268201500001C/HL/NHLBI NIH HHSUnited States/ ; P50 AG016574/AG/NIA NIH HHSUnited States/ ; P30 AG066511/AG/NIA NIH HHSUnited States/ ; U24 AG072122/AG/NIA NIH HHSUnited States/ ; HHSN268201100005G/HL/NHLBI NIH HHSUnited States/ ; P30 AG066512/AG/NIA NIH HHSUnited States/ ; U01 AG049507/AG/NIA NIH HHSUnited States/ ; U01 HL096917/HL/NHLBI NIH HHSUnited States/ ; HHSN268201100008I/HL/NHLBI NIH HHSUnited States/ ; U01 AG052411/AG/NIA NIH HHSUnited States/ ; R01 AG019085/AG/NIA NIH HHSUnited States/ ; U01 AG032984/AG/NIA NIH HHSUnited States/ ; P30 AG066515/AG/NIA NIH HHSUnited States/ ; U01 HL130114/HL/NHLBI NIH HHSUnited States/ ; HHSN268201100007C/HL/NHLBI NIH HHSUnited States/ ; P30 AG062421/AG/NIA NIH HHSUnited States/ ; HHSN268200800007C/HL/NHLBI NIH HHSUnited States/ ; R01 AG048234/AG/NIA NIH HHSUnited States/ ; U01 AG068057/AG/NIA NIH HHSUnited States/ ; HHSN268201100011I/HL/NHLBI NIH HHSUnited States/ ; HHSN268201100011C/HL/NHLBI NIH HHSUnited States/ ; RF1 AG054074/AG/NIA NIH HHSUnited States/ ; R01-AG076002/NH/NIH HHSUnited States/ ; P50 NS039764/NS/NINDS NIH HHSUnited States/ ; P30 AG066508/AG/NIA NIH HHSUnited States/ ; U01 HL096902/HL/NHLBI NIH HHSUnited States/ ; U24 AG056270/AG/NIA NIH HHSUnited States/ ; P30 AG072978/AG/NIA NIH HHSUnited States/ ; R01 AG017917/AG/NIA NIH HHSUnited States/ ; RC2 HG005605/HG/NHGRI NIH HHSUnited States/ ; R56 AG051876/AG/NIA NIH HHSUnited States/ ; P30 AG062429/AG/NIA NIH HHSUnited States/ ; P30 AG066519/AG/NIA NIH HHSUnited States/ ; R01 AG028786/AG/NIA NIH HHSUnited States/ ; N01HC55222/HL/NHLBI NIH HHSUnited States/ ; U54 HG003273/HG/NHGRI NIH HHSUnited States/ ; R01 AG049607/AG/NIA NIH HHSUnited States/ ; UF1 AG047133/AG/NIA NIH HHSUnited States/ ; U01 AG057659/AG/NIA NIH HHSUnited States/ ; U24 AG074855/AG/NIA NIH HHSUnited States/ ; RF1 AG054023/AG/NIA NIH HHSUnited States/ ; R01 AG054047/AG/NIA NIH HHSUnited States/ ; U19 AG068753/NH/NIH HHSUnited States/ ; R01 AG061155/AG/NIA NIH HHSUnited States/ ; P50 AG005136/AG/NIA NIH HHSUnited States/ ; P30 AG072973/AG/NIA NIH HHSUnited States/ ; NU38 CK000480/CK/NCEZID CDC HHSUnited States/ ; N01HC85086/HL/NHLBI NIH HHSUnited States/ ; R01 HL105756/HL/NHLBI NIH HHSUnited States/ ; P30 AG062422/AG/NIA NIH HHSUnited States/ ; U19 AG024904/AG/NIA NIH HHSUnited States/ ; R01 AG079280/AG/NIA NIH HHSUnited States/ ; U01 AG062943/AG/NIA NIH HHSUnited States/ ; RF1 AG051504/AG/NIA NIH HHSUnited States/ ; U01AG049506/HL/NHLBI NIH HHSUnited States/ ; RF1 AG058066/AG/NIA NIH HHSUnited States/ ; HHSN268201100006C/HL/NHLBI NIH HHSUnited States/ ; U24 AG041689/AG/NIA NIH HHSUnited States/ ; RF1 AG027161/AG/NIA NIH HHSUnited States/ ; R01 AG044829/AG/NIA NIH HHSUnited States/ ; P30 AG066462/AG/NIA NIH HHSUnited States/ ; HHSN268201200036C/HL/NHLBI NIH HHSUnited States/ ; P30 AG010161/AG/NIA NIH HHSUnited States/ ; P30 AG066530/AG/NIA NIH HHSUnited States/ ; R01 AG033193/AG/NIA NIH HHSUnited States/ ; U01 AG058589/AG/NIA NIH HHSUnited States/ ; HHSN268201100005I/HL/NHLBI NIH HHSUnited States/ ; R01 AG032990/AG/NIA NIH HHSUnited States/ ; R37 AG015473/AG/NIA NIH HHSUnited States/ ; U01 NS041588/NS/NINDS NIH HHSUnited States/ ; R01 NS080820/NS/NINDS NIH HHSUnited States/ ; R01 AG059716/AG/NIA NIH HHSUnited States/ ; HHSN268201500001I/HL/NHLBI NIH HHSUnited States/ ; U01 AG049508/AG/NIA NIH HHSUnited States/ ; P50 AG008012/AG/NIA NIH HHSUnited States/ ; U01 AG052410/AG/NIA NIH HHSUnited States/ ; U01 HL096814/HL/NHLBI NIH HHSUnited States/ ; P50 AG005133/AG/NIA NIH HHSUnited States/ ; P30 AG066509/AG/NIA NIH HHSUnited States/ ; U01 AG006781/AG/NIA NIH HHSUnited States/ ; R01 AG041797/AG/NIA NIH HHSUnited States/ ; K23 AG030944/AG/NIA NIH HHSUnited States/ ; RC4 AG039085/AG/NIA NIH HHSUnited States/ ; P20 AG068077/AG/NIA NIH HHSUnited States/ ; U01 AG062602/AG/NIA NIH HHSUnited States/ ; R01 NS029993/NS/NINDS NIH HHSUnited States/ ; P30 AG066546/AG/NIA NIH HHSUnited States/ ; R01 AG021547/AG/NIA NIH HHSUnited States/ ; P30 AG038072/AG/NIA NIH HHSUnited States/ ; R01 AG032289/AG/NIA NIH HHSUnited States/ ; R01 AG048927/AG/NIA NIH HHSUnited States/ ; U54 HG003079/HG/NHGRI NIH HHSUnited States/ ; R01 AG019757/AG/NIA NIH HHSUnited States/ ; U01AG049507/HL/NHLBI NIH HHSUnited States/ ; U01 AG052409/AG/NIA NIH HHSUnited States/ ; U01 AG046139/AG/NIA NIH HHSUnited States/ ; R01 AG033040/AG/NIA NIH HHSUnited States/ ; RF1 AG054052/AG/NIA NIH HHSUnited States/ ; R01 AG020098/AG/NIA NIH HHSUnited States/ ; R01 AG076002/AG/NIA NIH HHSUnited States/ ; P30 AG072977/AG/NIA NIH HHSUnited States/ ; P30 AG062677/AG/NIA NIH HHSUnited States/ ; N01HC85082/HL/NHLBI NIH HHSUnited States/ ; HHSN268201100009C/HL/NHLBI NIH HHSUnited States/ ; R01 HL070825/HL/NHLBI NIH HHSUnited States/ ; N01HC85083/HL/NHLBI NIH HHSUnited States/ ; R01 AG027944/AG/NIA NIH HHSUnited States/ ; HHSN268201100005C/HL/NHLBI NIH HHSUnited States/ ; P20 AG068024/AG/NIA NIH HHSUnited States/ ; P30 AG072958/AG/NIA NIH HHSUnited States/ ; R01 AG025259/AG/NIA NIH HHSUnited States/ ; RF1 AG057519/AG/NIA NIH HHSUnited States/ ; U01 HL096899/HL/NHLBI NIH HHSUnited States/ ; HHSN268201100007I/HL/NHLBI NIH HHSUnited States/ ; P30 AG062715/AG/NIA NIH HHSUnited States/ ; RF1 AG015473/AG/NIA NIH HHSUnited States/ ; U01 AG049506/AG/NIA NIH HHSUnited States/ ; P30 AG066506/AG/NIA NIH HHSUnited States/ ; P30 AG072976/AG/NIA NIH HHSUnited States/ ; WT_/Wellcome TrustUnited Kingdom/ ; R01 AG011101/AG/NIA NIH HHSUnited States/ ; P30 AG066468/AG/NIA NIH HHSUnited States/ ; R01 AG021136/AG/NIA NIH HHSUnited States/ ; P30 AG072931/AG/NIA NIH HHSUnited States/ ; P30 AG072947/AG/NIA NIH HHSUnited States/ ; U01 AG058635/AG/NIA NIH HHSUnited States/ ; RF1 AG057519/NH/NIH HHSUnited States/ ; N01HC85079/HL/NHLBI NIH HHSUnited States/ ; P30 AG072972/AG/NIA NIH HHSUnited States/ ; R01 AG023629/AG/NIA NIH HHSUnited States/ ; P30 AG066514/AG/NIA NIH HHSUnited States/ ; U19 AG066567/AG/NIA NIH HHSUnited States/ ; N01HC85080/HL/NHLBI NIH HHSUnited States/ ; P30 AG072959/AG/NIA NIH HHSUnited States/ ; R01 AG031272/AG/NIA NIH HHSUnited States/ ; R01 AG011380/AG/NIA NIH HHSUnited States/ ; P50 NS071674/NS/NINDS NIH HHSUnited States/ ; U19 AG068753/AG/NIA NIH HHSUnited States/ ; P30 AG072979/AG/NIA NIH HHSUnited States/ ; RF1 AG058267/AG/NIA NIH HHSUnited States/ ; R01 AG015819/AG/NIA NIH HHSUnited States/ ; N01HC85081/HL/NHLBI NIH HHSUnited States/ ; U01 AG062602/NH/NIH HHSUnited States/ ; U01 AG049505/AG/NIA NIH HHSUnited States/
• Volume:
  20
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:8c03a8f06bdb67f17f5ea3677627e87ee474f445c944a45e66676093400cf2bb8fddfcab315dcdafd6b1203963627150d456122cfd06101458bf99a6c7435557
• Download URL:
  https://stacks.cdc.gov/view/cdc/147687/cdc_147687_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]