Myasthenia gravis is a multifactorial disease that is thought to be caused by environmental factors in people with a genetic predisposition. A new international study confirms this hypothesis. Based on genome-wide association study (GWAS) and pantranscriptomic (TWAS) explorations of 1,873 patients with myasthenia gravis with autoantibodies to acetylcholine receptors (AChR) and 36,370 disease-free individuals, this work confirms the involvement of genetic factors already identified as risk factors (PTPN22, HLA-DQA1/HLA-B and TNFRSF11A) and identifies new ones:
- the genes encoding the nicotinic alpha 1 (CHRNA1) and beta 1 (CHRNB1) subunits of the cholinergic receptor, among which certain variants would lead to under-expression of their respective subunits
- the ERBB2 gene, which encodes a protein regulating the expression of the subunits of the acetylcholine receptor and is said to be under-expressed in the muscles of people with myasthenia.
The study also found common genetic characteristics between myasthenia and other autoimmune diseases (hypothyroidism, rheumatoid arthritis, type 1 diabetes, etc.), and conversely, distinctive genetic profiles between its early-onset and late-onset forms.
