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
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

26331055231166411

Informations 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.

Références

Schizophr Res. 2010 May;118(1-3):224-31
pubmed: 20153952
Nucleic Acids Res. 2020 Jan 8;48(D1):D948-D955
pubmed: 31667505
Psychopharmacology (Berl). 2019 Oct;236(10):2909-2921
pubmed: 30756134
Schizophr Bull. 2015 Mar;41 Suppl 2:S408-16
pubmed: 25810055
Nature. 2016 Feb 11;530(7589):177-83
pubmed: 26814963
Schizophr Bull. 2013 Nov;39(6):1174-9
pubmed: 24072812
J Theor Biol. 1995 Aug 7;175(3):373-88
pubmed: 7475081
Transl Psychiatry. 2015 Jul 28;5:e608
pubmed: 26218850
Tissue Antigens. 2014 May;83(5):350-5
pubmed: 24666112
J Postgrad Med. 2019 Jul-Sep;65(3):141-145
pubmed: 31169131
Nature. 2009 Aug 6;460(7256):744-7
pubmed: 19571808
Biol Psychiatry. 2011 Oct 1;70(7):696-8
pubmed: 21514568
Sci Rep. 2022 May 16;12(1):8074
pubmed: 35577837
Clin Microbiol Rev. 2009 Apr;22(2):370-85, Table of Contents
pubmed: 19366919
Science. 2018 Jun 22;360(6395):
pubmed: 29930110
Curr Res Transl Med. 2020 Nov;68(4):211-216
pubmed: 32624427
Cancer Inform. 2023 Jan 16;22:11769351221148588
pubmed: 36684415
Eur J Hum Genet. 2008 Dec;16(12):1413-29
pubmed: 19020537
Am J Psychiatry. 2013 Aug;170(8):877-85
pubmed: 23903335
CNS Drugs. 2006;20(11):879-85
pubmed: 17044725
Am J Med Genet B Neuropsychiatr Genet. 2014 Jan;165B(1):19-27
pubmed: 24142843
Nat Genet. 2011 Sep 18;43(10):969-76
pubmed: 21926974
Acta Psychiatr Scand. 2018 Nov;138(5):464-471
pubmed: 29869414
Schizophr Bull. 2015 Mar;41 Suppl 2:S366-73
pubmed: 25548387
Psychol Med. 2021 Oct;51(13):2168-2177
pubmed: 33550997
Clin Infect Dis. 2006 Nov 1;43(9):1143-51
pubmed: 17029132
Annu Rev Genomics Hum Genet. 2013;14:301-23
pubmed: 23875801
Philos Trans R Soc Lond B Biol Sci. 1994 Nov 29;346(1317):379-85
pubmed: 7708832
Am J Psychiatry. 2006 Mar;163(3):521-8
pubmed: 16513876
Nucleic Acids Res. 2020 Jul 2;48(W1):W449-W454
pubmed: 32406916
Schizophr Res. 2019 Jul;209:40-47
pubmed: 30639164
Am J Psychiatry. 2014 Feb;171(2):218-26
pubmed: 24129899
World J Gastroenterol. 2007 Mar 28;13(12):1770-87
pubmed: 17465466
Mol Psychiatry. 2022 Mar;27(3):1448-1454
pubmed: 34799693
J R Soc Med. 2004 Jan;97(1):10-4
pubmed: 14702356
PLoS Biol. 2022 Jun 1;20(6):e3001687
pubmed: 35648781
Mol Psychiatry. 2012 Dec;17(12):1228-38
pubmed: 22488257
Am J Psychiatry. 2019 Oct 1;176(10):846-855
pubmed: 31416338
PLoS Med. 2005 May;2(5):e141
pubmed: 15916472
Front Genet. 2021 Jun 28;12:686666
pubmed: 34262598
Lancet Psychiatry. 2015 Mar;2(3):258-270
pubmed: 26359903
Arch Gen Psychiatry. 2003 Dec;60(12):1187-92
pubmed: 14662550
NCHS Data Brief. 2018 Feb;(304):1-8
pubmed: 29442994
Bull World Health Organ. 2020 May 01;98(5):315-329
pubmed: 32514197
Mol Psychiatry. 2007 Jan;12(1):105-13, 1
pubmed: 17033628
Ann N Y Acad Sci. 2012 Jul;1262:56-66
pubmed: 22823436
Neurosci Biobehav Rev. 2014 Jan;38:72-93
pubmed: 24247023
Hum Hered. 2011;72(3):161-72
pubmed: 22004985
Hum Antibodies. 2018 Feb 5;26(2):87-93
pubmed: 29036805
Schizophr Bull. 2018 Oct 17;44(6):1195-1203
pubmed: 29762765
Annu Rev Immunol. 2013;31:443-73
pubmed: 23298205
Ann Med. 2007;39(2):145-53
pubmed: 17453677
Schizophr Res. 2012 Apr;136(1-3):128-36
pubmed: 22104141
Neurosci Biobehav Rev. 2016 Jun;65:185-94
pubmed: 27073049
Nature. 1970 Aug 1;227(5257):520-1
pubmed: 5428476
Nat Rev Immunol. 2018 May;18(5):325-339
pubmed: 29292391
Am J Psychiatry. 2003 Dec;160(12):2234-6
pubmed: 14638597
Immunology. 2017 Nov;152(3):388-401
pubmed: 28704576
Schizophr Res. 2008 Dec;106(2-3):268-74
pubmed: 18801645
Front Aging Neurosci. 2019 Apr 12;11:82
pubmed: 31031617
Schizophr Res. 2001 Jan 15;47(1):1-12
pubmed: 11163540
Genetics. 1999 May;152(1):393-400
pubmed: 10224269
Hepatology. 2001 Jun;33(6):1512-7
pubmed: 11391541
Nature. 2009 Aug 6;460(7256):748-52
pubmed: 19571811
Nature. 2009 Aug 6;460(7256):753-7
pubmed: 19571809
PLoS One. 2012;7(7):e41400
pubmed: 22848484
Psychiatry Res. 2020 Sep;291:113157
pubmed: 32593064
Clin Microbiol Rev. 1995 Jan;8(1):131-45
pubmed: 7704891
Schizophr Res. 2007 Aug;94(1-3):342-53
pubmed: 17561376
J Psychiatr Res. 1999 Nov-Dec;33(6):543-8
pubmed: 10628531
BMJ Glob Health. 2020 Jul;5(7):
pubmed: 32675066
Am J Psychiatry. 2011 Dec;168(12):1303-10
pubmed: 22193673
Brain Behav Immun. 2015 May;46:311-8
pubmed: 25728236
Malar J. 2014 Sep 03;13:349
pubmed: 25187124
Biol Psychiatry. 2012 Oct 15;72(8):620-8
pubmed: 22883433
J Autoimmun. 2015 Nov;64:13-25
pubmed: 26142251
Arch Gen Psychiatry. 2003 May;60(5):466-72
pubmed: 12742867
Neurosci Insights. 2022 Jul 22;17:26331055221114817
pubmed: 35910083
Acta Psychiatr Scand. 2017 Oct;136(4):409-423
pubmed: 28832904
Psicothema. 2021 Feb;33(1):16-27
pubmed: 33453732
Schizophr Bull. 2012 Nov;38(6):1137-48
pubmed: 22490995
Schizophr Bull. 2012 Nov;38(6):1149-54
pubmed: 22966150
J Nerv Ment Dis. 2018 Mar;206(3):173-178
pubmed: 29474231
Prog Neurobiol. 2011 Jan;93(1):23-58
pubmed: 20955757
Schizophr Bull. 2014 Nov;40(6):1552-9
pubmed: 24714379
Psychol Med. 2013 Feb;43(2):239-57
pubmed: 22717193
Psychol Med. 1986 Nov;16(4):757-63
pubmed: 3029788
Am J Psychiatry. 2010 Mar;167(3):261-80
pubmed: 20123911
Philos Trans R Soc Lond B Biol Sci. 2012 Mar 19;367(1590):830-9
pubmed: 22312050
Schizophr Bull. 2018 Aug 20;44(5):973-982
pubmed: 29648618
Schizophr Res. 2012 Aug;139(1-3):161-8
pubmed: 22704639
Psychol Bull. 1992 Jul;112(1):155-9
pubmed: 19565683
Br J Psychiatry. 2012 May;200(5):374-80
pubmed: 22442099

Auteurs

Lisa M James (LM)

The HLA Research Group, Department of Veterans Affairs Health Care System, Brain Sciences Center, Minneapolis, MN, USA.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA.
Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA.

Spyros A Charonis (SA)

The HLA Research Group, Department of Veterans Affairs Health Care System, Brain Sciences Center, Minneapolis, MN, USA.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA.

Apostolos P Georgopoulos (AP)

The HLA Research Group, Department of Veterans Affairs Health Care System, Brain Sciences Center, Minneapolis, MN, USA.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA.
Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA.
Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.

Classifications MeSH