Schizophrenia, Human Leukocyte Antigen (HLA), and Herpes Viruses: Immunogenetic Associations at the Population Level.
HHV1
Human leukocyte antigen
epidemiology
immunogenetics
schizophrenia
Journal
Neuroscience insights
ISSN: 2633-1055
Titre abrégé: Neurosci Insights
Pays: United States
ID NLM: 101760670
Informations de publication
Date de publication:
2023
2023
Historique:
received:
24
10
2022
accepted:
13
03
2023
medline:
20
4
2023
pubmed:
20
4
2023
entrez:
20
04
2023
Statut:
epublish
Résumé
Several factors have been implicated in schizophrenia (SZ), including human herpes viruses (HHV) and the adaptive immunity Human Leukocyte Antigen (HLA) genes. Here we investigated these issues in 2 complementary ways. In one analysis, we evaluated SZ-HLA and HHV-HLA associations at the level of a single allele by computing (a) a SZ-HLA protection/susceptibility (P/S) score based on the covariance between SZ and 127 HLA allele prevalences in 14 European countries, (b) estimating in silico HHV-HLA best binding affinities for the 9 HHV strains, and (c) evaluating the dependence of P/S score on HHV-HLA binding affinities. These analyses yielded (a) a set of 127 SZ-HLA P/S scores, varying by >200× (maximum/minimum), which could not be accounted for by chance, (b) a set of 127 alleles × 9 HHV best-estimated affinities, varying by >600×, and (c) a set of correlations between SZ-HLA P/S scores and HHV-HLA binding which indicated a prominent role of HHV1. In a subsequent analysis, we extended these findings to the individual person by taking into account the fact that every individual carries 12 HLA alleles and computed (a) the average SZ-HLA P/S scores of 12 randomly chosen alleles (2 per gene), an indicator of HLA-based SZ P/S for an individual, and (b) the average of the corresponding HHV estimated affinities for those alleles, an indicator of overall effectiveness of HHV-HLA binding. We found (a) that HLA protection for SZ was significantly more prominent than susceptibility, and (b) that protective SZ-HLA scores were associated with higher HHV-HLA binding affinities, indicating that HLA binding and subsequent elimination of several HHV strains may confer protection against schizophrenia.
Identifiants
pubmed: 37077512
doi: 10.1177/26331055231166411
pii: 10.1177_26331055231166411
pmc: PMC10108429
doi:
Types de publication
Journal Article
Langues
eng
Pagination
26331055231166411Informations de copyright
© The Author(s) 2023.
Déclaration de conflit d'intérêts
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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