Elucidating genetic backgrounds of myasthenia gravis in Japanese by genome-wide association studies and multi-omics analyses of thymoma - PubMed
a day ago
- #TERT gene
- #myasthenia gravis
- #genome-wide association study
- Genome-wide association study (GWAS) of 1,434 myasthenia gravis (MG) cases and 42,913 controls in Japanese population identifies the TERT locus as a new genetic association (OR = 1.31, P = 1.7×10-10).
- Subtype-stratified GWASs reveal stronger associations for generalized MG (gMG), anti-AChR antibody-positive gMG (g-AChR-Ab(+)MG), and thymoma-associated gMG (g-TAMG).
- Fine-mapping of the MHC region shows distinct HLA associations: HLA-DRB1 with late-onset gMG (g-LOMG) and HLA-A with early-onset gMG (g-EOMG).
- The TERT lead variant rs2736099 is linked to poor treatment response, particularly in g-AChR-Ab(+)MG and g-EOMG (P < 0.0042).
- Phenome-wide association study identifies pleiotropic effects of TERT on lung cancer, hematological traits, and telomere length.
- Single-cell transcriptomics and immunohistochemistry show immature lymphocyte-specific TERT expression in thymoma.
- Full-length transcriptomics indicate allele-specific decreasing effect of rs2736099-A on TERT expression.
- The study highlights distinct genetic backgrounds of MG subtypes and the role of TERT in pathogenesis.