The predisposition to myasthenia gravis is becoming better known

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.


Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study. Chia R, Saez-Atienzar S, Murphy N et al. Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2108672119.