Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study

著者: Ruth Chia, Sara Sáez-Atiénzar, Natalie A. Murphy, Adriano Chiò, Cornelis Blauwendraat, Ricardo H. Roda, Pentti J. Tienari, Henry J. Kaminski, Roberta Ricciardi, Melania Guida, Anna De Rosa, Loredana Petrucci, Amelia Evoli, Carlo Provenzano, Daniel B. Drachman, Bryan J. Traynor, Yevgeniya Abramzon, Richard J. Barohn, Michael Benatar, Derrick Blackmore, Vinay Chaudhry, Adriano Chiò, Manisha Chopra, Andrea M. Corse, Anna De Rosa, Mazen M. Dimachkie, Amelia Evoli, Julaine Florence, Miriam Freimer, Melania Guida, James F. Howard, Theresa Jiwa, Henry J. Kaminski, John T. Kissel, Wilma J. Koopman, Bernadette Lipscomb, Michelangelo Maestri, Mariapaola Marino, Janice M. Massey, April McVey, Michelle M. Mezei, Srikanth Muppidi, Michael Nicolle, Joël Oger, Robert M. Pascuzzi, Mamatha Pasnoor, Alan Pestronk, Loredana Petrucci, Hannah A. Pliner, Carlo Provenzano, Alan E. Renton, Roberta Ricciardi, David P. Richman, Julie Rowin, Donald B. Sanders, Mario Sabatelli, Zaeem A. Siddiqi, Aimee Soloway, Laura Todi, Gil I. Wolfe, Charlie Wulf, Daniel B. Drachman, Bryan J. Traynor - Proceedings of the National Academy of Sciences, PNAS 2022 被引用: 132

were confirmed. Subgroup analyses demonstrate that early- and late-onset cases have different genetic risk factors. Genetic correlation analysis confirmed a genetic link between myasthenia gravis and other autoimmune diseases, such as hypothyroidism, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. Finally, we applied Priority Index analysis to identify potentially druggable genes/proteins and pathways. This study provides insight into the genetic architecture underlying myasthenia gravis and demonstrates that genetic factors within the loci encoding acetylcholine receptor subunits contribute to its pathogenesis.