Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study-Reference-Cited by-同舟云学术

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

Published:2022-01-24 Issue:5 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Chia Ruth¹^ORCID,Saez-Atienzar Sara¹^ORCID,Murphy Natalie¹,Chiò Adriano²³⁴,Blauwendraat Cornelis⁵,Roda Ricardo H.⁶,Tienari Pentti J.⁷⁸^ORCID,Kaminski Henry J.⁹,Ricciardi Roberta¹⁰,Guida Melania¹⁰^ORCID,De Rosa Anna¹⁰^ORCID,Petrucci Loredana¹⁰,Evoli Amelia¹¹^ORCID,Provenzano Carlo¹²^ORCID,Drachman Daniel B.⁶,Traynor Bryan J.¹⁶¹³¹⁴^ORCID,Abramzon Yevgeniya,Barohn Richard J.,Benatar Michael,Blackmore Derrick,Chaudhry Vinay,Chiò Adriano,Chopra Manisha,Corse Andrea,Rosa Anna De,Dimachkie Mazen M.,Evoli Amelia,Florence Julaine,Freimer Miriam,Guida Melania,Howard James F.,Jiwa Theresa,Kaminski Henry J.,Kissel John T.,Koopman Wilma J.,Lipscomb Bernadette,Maestri Michelangelo,Marino Mariapaola,Massey Janice M.,McVey April,Mezei Michelle M.,Muppidi Srikanth,Nicolle Michael W.,Oger Joel,Pascuzzi Robert M.,Pasnoor Mamatha,Pestronk Alan,Petrucci Loredana,Pliner Hannah A.,Provenzano Carlo,Renton Alan E.,Ricciardi Roberta,Richman David P.,Rowin Julie,Sanders Donald B.,Sabatelli Mario,Siddiqi Zaeem,Soloway Aimee,Todi Laura,Wolfe Gil,Wulf Charlie,Drachman Daniel B.,Traynor Bryan J.,

Affiliation:

1. Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892

2. Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin 10126, Italy

3. Institute of Cognitive Sciences and Technologies, Consiglio Nazionale delle Ricerche, Rome 00185, Italy

4. Neurology 1, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin 10126, Italy

5. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892

6. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287

7. Department of Neurology, Neurocenter, Helsinki University Hospital, Helsinki FIN-02900, Finland

8. Research Program of Translational Immunology, Faculty of Medicine, University of Helsinki, Helsinki FIN-02900, Finland

9. Department of Neurology and Rehabilitation Medicine, George Washington University, Washington, DC 20037

10. Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy

11. Institute of Neurology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome 00168, Italy

12. Dipartimento di Medicina e chirurgia traslazionale, Sezione di Patologia generale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome 00168, Italy

13. Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK

14. National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892

Abstract

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, namely CHRNA1 and CHRNB1 , 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.

Funder

HHS | NIH | National Institute on Aging

Myasthenia Gravis Foundation of America

Bequest fund from Geraldine Weinrib

Bequest fund from Philip Swift

Bequest fund from Mr. and Mrs. Don Brandon

Philanthropic support from Dr. Peter Buck

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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