Academic Journal
Bayesian colocalization of psychiatric disorder GWAS signals with molecular quantitative trait loci highlights histone involvement and neuroimmune dysregulation in pathogenesis.
| Τίτλος: | Bayesian colocalization of psychiatric disorder GWAS signals with molecular quantitative trait loci highlights histone involvement and neuroimmune dysregulation in pathogenesis. |
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| Συγγραφείς: | Ryu J; School of Systems Biomedical Science and Integrative Institute of Basic Science, Soongsil University, 369 Sangdo-ro, Dongjak-gu, Seoul 06978, South Korea., Lee C; School of Systems Biomedical Science and Integrative Institute of Basic Science, Soongsil University, 369 Sangdo-ro, Dongjak-gu, Seoul 06978, South Korea. Electronic address: clee@ssu.ac.kr. |
| Πηγή: | Psychiatry research [Psychiatry Res] 2026 Oct; Vol. 364, pp. 117287. Date of Electronic Publication: 2026 Jun 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Ireland NLM ID: 7911385 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7123 (Electronic) Linking ISSN: 01651781 NLM ISO Abbreviation: Psychiatry Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier/North-Holland Biomedical Press Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| Ιατρικοί όροι (MeSH): | Quantitative Trait Loci*/genetics , Histones*/genetics , Histones*/metabolism , Mental Disorders*/genetics , Mental Disorders*/immunology , Mental Disorders*/metabolism , Neuroimmunomodulation*/genetics , Genome-Wide Association Study*, Schizophrenia/genetics ; Schizophrenia/immunology ; Major Depressive Disorder/genetics ; Major Depressive Disorder/immunology ; Bipolar Disorder/genetics ; Bipolar Disorder/immunology ; Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/immunology ; Attention Deficit Disorder with Hyperactivity/genetics ; Attention Deficit Disorder with Hyperactivity/immunology ; Humans ; Bayes Theorem ; Genetic Predisposition to Disease |
| Περίληψη: | Genome-wide association studies (GWAS) have revolutionized our understanding of the genetic architecture of psychiatric disorders. However, the interpretation of these findings remains challenging, as most risk loci reside in non-coding regions, obscuring the underlying molecular mechanisms. To elucidate the functional consequences of psychiatric risk variants, we implemented a multi-omics Bayesian colocalization framework using transcript, protein and metabolite levels for attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ). Sixty-five SCZ, BIP, and MDD GWAS signals colocalized with immune cell-type-specific expression quantitative trait loci (eQTL), targeting 70 genes. Notably, they included 17 histone-encoding genes colocalized from five GWAS signals. These signals subsequently colocalized with protein QTL (pQTL), targeting 310 proteins enriched in various immune-related pathways (P < 5.99 × 10⁻12). Further colocalization with metabolite QTL (metabQTL) revealed 23 metabolites, highlighting GABAergic neurotransmission, norepinephrine metabolism, and androgenic neurosteroid pathways. Considering critical histone function as damage-associated molecular patterns, variability in histone expression might have contributed to neuroimmune mechanisms and thus the pathogenesis of the psychiatric disorders. This study underscores the role of common nucleotide variants regulating histone genes in neuroimmune mechanisms contributing to SCZ, BIP, and MDD. These findings enhance our understanding of underlying molecular targets in their pathophysiology, with a potential strategy of precision psychiatry. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Bipolar disorder; Colocalization; GABAergic neurotransmission; Histone; Major depressive disorder; Molecular quantitative trait loci; Schizophrenia |
| Substance Nomenclature: | 0 (Histones) |
| Entry Date(s): | Date Created: 20260619 Date Completed: 20260810 Latest Revision: 20260810 |
| Update Code: | 20260811 |
| DOI: | 10.1016/j.psychres.2026.117287 |
| PMID: | 42320287 |
| Βάση Δεδομένων: | MEDLINE |
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