Academic Journal
Causal Variants in CHRNA1 and CHRNB1 Genes for Anti-acetylcholine Receptor Antibody Positive Myasthenia Gravis: Evidence from Bayesian Fine-Mapping and Genetic Association Study.
| Τίτλος: | Causal Variants in CHRNA1 and CHRNB1 Genes for Anti-acetylcholine Receptor Antibody Positive Myasthenia Gravis: Evidence from Bayesian Fine-Mapping and Genetic Association Study. |
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| Συγγραφείς: | Garai N; University of Belgrade-Faculty of Biology, Center for Human Molecular Genetics, Studentski Trg 16, 11158, Belgrade, Serbia., Petrovic K; Institute of Chemistry, Technology and Metallurgy, Njegoseva 12, 11000, Belgrade, Serbia., Peric S; University Clinical Center of Serbia, Neurology Clinic, Dr Subotica Starijeg 6, 11000, Belgrade, Serbia.; University of Belgrade-Faculty of Medicine, Dr Subotica Starijeg 8, 11000, Belgrade, Serbia., Djordjevic I; University Clinical Center of Serbia, Neurology Clinic, Dr Subotica Starijeg 6, 11000, Belgrade, Serbia., Pesovic J; University of Belgrade-Faculty of Biology, Center for Human Molecular Genetics, Studentski Trg 16, 11158, Belgrade, Serbia., Brkusanin M; University of Belgrade-Faculty of Biology, Center for Human Molecular Genetics, Studentski Trg 16, 11158, Belgrade, Serbia., Brajuskovic G; University of Belgrade-Faculty of Biology, Center for Human Molecular Genetics, Studentski Trg 16, 11158, Belgrade, Serbia., Lavrnic D; University Clinical Center of Serbia, Neurology Clinic, Dr Subotica Starijeg 6, 11000, Belgrade, Serbia.; University of Belgrade-Faculty of Medicine, Dr Subotica Starijeg 8, 11000, Belgrade, Serbia., Apostolski S; Outpatient Neurological Clinic 'Apostolski', Vojislava Ilica 100, 11010, Belgrade, Serbia., Basta I; University Clinical Center of Serbia, Neurology Clinic, Dr Subotica Starijeg 6, 11000, Belgrade, Serbia.; University of Belgrade-Faculty of Medicine, Dr Subotica Starijeg 8, 11000, Belgrade, Serbia., Jovanovic VM; Department for Biology, Chemistry and Pharmacy-Human Biology and Primate Evolution, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany., Savic-Pavicevic D; University of Belgrade-Faculty of Biology, Center for Human Molecular Genetics, Studentski Trg 16, 11158, Belgrade, Serbia. duska@bio.bg.ac.rs. |
| Πηγή: | Molecular neurobiology [Mol Neurobiol] 2025 Sep; Vol. 62 (9), pp. 11286-11296. Date of Electronic Publication: 2025 Apr 25. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Humana Press Country of Publication: United States NLM ID: 8900963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1182 (Electronic) Linking ISSN: 08937648 NLM ISO Abbreviation: Mol Neurobiol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Clifton, NJ : Humana Press, c1987- |
| Ιατρικοί όροι (MeSH): | Receptors, Nicotinic*/genetics , Myasthenia Gravis*/genetics , Myasthenia Gravis*/immunology , Polymorphism, Single Nucleotide*/genetics , Autoantibodies*/immunology , Genetic Predisposition to Disease* , Genetic Association Studies* , Chromosome Mapping*, Linkage Disequilibrium/genetics ; Humans ; Bayes Theorem ; Female ; Male ; Genome-Wide Association Study ; Middle Aged ; Adult |
| Περίληψη: | Autoantibodies target the acetylcholine receptor (AChR) in 85% of myasthenia gravis (MG) patients. Genomic studies highlighted the association of genes encoding AChR subunits (CHRNA1 and CHRNB1) and MG in European populations. Additionally, Mendelian randomization revealed rs4151121 at the CHRNB1 locus as a potential causal variant. Here, we performed Bayesian fine-mapping of the CHRNA1 locus using GWAS summary statistics, a linkage disequilibrium matrix and functional annotations. The GWAS lead hit rs35274388 was identified as a causal variant overlapping with the promoter region (p < 0.01). Next, we performed a candidate gene study including 1038 participants from Serbia. Rs4151121 minor allele G was associated with late-onset MG (LOMG) (OR = 1.327, 95% CI = 1.084-1.625, p = 0.006, p (© 2025. The Author(s).) |
| Competing Interests: | Declarations. Ethics Approval and Consent to Participate: The study was approved by the Ethical Board of the University Clinical Center of Serbia (No.187/14). This study was performed in line with the principles of the Declaration of Helsinki. After a detailed discussion on the objectives and requirements of the study, written informed consent was obtained from all study participants. Consent for Publication: Not applicable. Competing interests: The authors declare no competing interests. |
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| Grant Information: | Agreement No. 451-03-65/2024-01 and Agreement No. 451-03-66/2024-03 The Ministry of Science, Technological Development and Innovations of the Republic of Serbia |
| Contributed Indexing: | Keywords: CHRNA1; CHRNB1; Autoimmune disease; Bayesian fine-mapping; Myasthenia Gravis; Single-nucleotide variants |
| Substance Nomenclature: | 0 (Receptors, Nicotinic) 0 (CHRNA1 protein, human) 0 (Autoantibodies) |
| Entry Date(s): | Date Created: 20250425 Date Completed: 20250820 Latest Revision: 20250823 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12367955 |
| DOI: | 10.1007/s12035-025-04958-7 |
| PMID: | 40279038 |
| Βάση Δεδομένων: | MEDLINE |
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