Open AccessIdentification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study
Author(s) -
Ruth Chia,
Sara Sáez-Atiénzar,
Natalie A. Murphy,
Adriano Chiò,
Cornelis Blauwendraat,
Ricardo H. Roda,
Pentti J. Tienari,
Henry J. Kaminski,
Rocco Ricciardi,
Melania Guida,
Anna De Rosa,
Loredana Petrucci,
Amelia Evoli,
Carlo Provenzano,
Daniel B. Drachman,
Bryan J. Traynor,
AUTHOR_ID
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2108672119
Subject(s) - myasthenia gravis , genome wide association study , acetylcholine receptor , biology , genetic association , genetics , single nucleotide polymorphism , immunology , gene , receptor , genotype
Significance Our study, involving 1,873 patients and 36,370 healthy individuals, is an extensive genome-wide study of myasthenia gravis. Our genome-wide association and transcriptome-wide association analyses identified two signals, namelyCHRNA1 andCHRNB1 , encoding acetylcholine receptor subunits, which were replicated in an independent cohort obtained from the UK Biobank. Identifying these genes confirms the potential utility of using genetics to identify proteins that are the antigenic targets of autoantibodies. We confirmed that the genetic abnormalities underlying early-onset and late-onset myasthenia gravis are different. Our data offer a broader insight into the genetic architecture underlying the pathophysiology of myasthenia gravis.