Identification of new NMOSD and MOGAD genetic associations - Archive ouverte HAL
Poster De Conférence Année : 2023

Identification of new NMOSD and MOGAD genetic associations

Nicolas Vince (1) , Irène Charles (1) , Sonia Bourguiba-Hachemi (1) , Sandra Vukusic (2, 3, 4, 5) , Lakhdar Banyahya (3, 5) , Françoise Durand-Dubief (5, 3) , François Cotton (6, 7) , Thi Hélène Zéphyr (8, 9) , Elisabeth Maillart (10, 11) , Caroline Papeix (12, 10, 11) , Bertrand Audoin (13, 14) , Xavier Ayrignac (15, 16) , Bertrand Bourre (17) , Jonathan Ciron (18) , Mikael Cohen (19, 20) , Nicolas Collongues (21, 22) , Romain Deschamps (12) , Aurélie Ruet (23, 24) , Eric Thouvenot (25, 26) , Romain Marignier (2, 3, 4, 5) , Sophie Limou (1) , Pierre-Antoine Gourraud (1) , David‐axel Laplaud (1)
1 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
2 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
3 Service de Neurologie [Lyon]
4 Fondation Eugène Devic EDMUS
5 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
6 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
7 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
8 LilNCog - Lille Neurosciences & Cognition - U 1172
9 CRC-SEP Nord-Pas de Calais - Centre de Ressources et de Compétences sur la Sclérose en Plaques (CRC-SEP) [Lille]
10 CHU Pitié-Salpêtrière [AP-HP]
11 MIRCEM - Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle
12 Hôpital Fondation Adolphe de Rothschild = Adolphe de Rothschild Foundation Hospital
13 INT - Institut de Neurosciences de la Timone
14 TIMONE - Hôpital de la Timone [CHU - APHM]
15 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
16 INM - Institut des Neurosciences de Montpellier
17 CHU Rouen
18 CRC-SEP Toulouse - Centre Ressources et Compétences sclérose en plaques (CRC-SEP) [CHU Toulouse]
19 CHU Nice - Centre Hospitalier Universitaire de Nice
20 URRIS UR2CA - Unité de Recherche Clinique de la Côte d’Azur
21 Service de Neurologie [Strasbourg]
22 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
23 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
24 Service de neurologie [Bordeaux]
25 IGF - Institut de Génomique Fonctionnelle
26 Pôle NIRR - Service de Neurologie [CHU Nimes]
Nicolas Vince
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
Irène Charles
  • Fonction : Auteur
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
Sonia Bourguiba-Hachemi
  • Fonction : Auteur
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
Sandra Vukusic
Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
Service de Neurologie [Lyon]
Fondation Eugène Devic EDMUS
Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Lakhdar Banyahya
  • Fonction : Auteur
Service de Neurologie [Lyon]
Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Françoise Durand-Dubief
Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Service de Neurologie [Lyon]
François Cotton
Centre Hospitalier Lyon Sud [CHU - HCL]
Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
Thi Hélène Zéphyr
  • Fonction : Auteur
Lille Neurosciences & Cognition - U 1172
Centre de Ressources et de Compétences sur la Sclérose en Plaques (CRC-SEP) [Lille]
Elisabeth Maillart
CHU Pitié-Salpêtrière [AP-HP]
Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle
Caroline Papeix
Hôpital Fondation Adolphe de Rothschild = Adolphe de Rothschild Foundation Hospital
CHU Pitié-Salpêtrière [AP-HP]
Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle
Bertrand Audoin
Institut de Neurosciences de la Timone
Hôpital de la Timone [CHU - APHM]
Xavier Ayrignac
Centre Hospitalier Régional Universitaire [Montpellier]
Institut des Neurosciences de Montpellier
Bertrand Bourre
CHU Rouen
Jonathan Ciron
Centre Ressources et Compétences sclérose en plaques (CRC-SEP) [CHU Toulouse]
Mikael Cohen
Centre Hospitalier Universitaire de Nice
Unité de Recherche Clinique de la Côte d’Azur
Nicolas Collongues
Service de Neurologie [Strasbourg]
CIC Strasbourg
Romain Deschamps
Hôpital Fondation Adolphe de Rothschild = Adolphe de Rothschild Foundation Hospital
Aurélie Ruet
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
Service de neurologie [Bordeaux]
Eric Thouvenot
Institut de Génomique Fonctionnelle
Service de Neurologie [CHU Nimes]
CV
Romain Marignier
Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
Service de Neurologie [Lyon]
Fondation Eugène Devic EDMUS
Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Sophie Limou
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
Pierre-Antoine Gourraud
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
David‐axel Laplaud
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology

Résumé

Introduction: Neuromyelitis Optica Spectrum Disorder (NMOSD) is a severe autoimmune demyelinating disease of the optic nerves and spinal cord affecting 0.4-4/100,000 individuals worldwide. Recently, an international consensus was reached to harmonize diagnosis criteria of neuroinflammatory diseases. The majority of patients with NMOSD are positive for a specific auto-antibody against the astrocytic aquaporin-4 (AQP4) water channel. A separate entity named MOGAD (MOG antibody-associated disease) groups patients with antibodies directed against the myelin oligodendrocyte glycoprotein (MOG). Two studies explored the genomic signature of NMOSD to date: 215 patients vs. 1244 controls from the USA and 203 patients vs. 1782 controls from Japan. They both found SNPs associated with NMOSD (AQP4) risk around HLA-DRB1 gene. However, only a few MOGAD patients were included in these GWASs, consequently, there is no formal GWAS about MOGAD to date. Objectives/Aims: To identify new genetic associations with NMOSD and MOGAD patients. Methods: DNA from 663 NMOSD and MOGAD patients (French NOMADMUS registry) was extracted and genotyped on the PMRA Affymetrix® Axiom chip (900k SNPs). After careful quality controls, we selected 656 patients with high-confidence genotypes. Results: We analyzed the genetic structure using a principal component analysis (PCA) to determine the ancestry of our patients. We could determine that a majority of our samples were of European ancestry (70%). We restricted our study to this population as other ancestries did not bear enough samples to perform a sufficiently powered analysis. We performed a GWAS comparing these patients to 1544 controls from France. We identified a SNP within the HLA class II genomic region to be significantly associated with NMOSD (AQP4) patients (P=1.1x10-9, OR 3.3) which is in line with previous studies. In addition, we found a novel SNP close to the MAP3K7 gene in chromosome 6 showing a suggestive association with MOGAD patients (P=3.9x10-7, OR 3.1). Conclusion: These preliminary results are very promising; however, additional analyses are needed to better describe these associations. We need to perform SNPs imputation to fine-map the genetic associations. We also need to impute the HLA to pinpoint associated HLA alleles, especially in NMOSD AQP4+ patients. This study is of great importance to better understand the genetic interplay between these neuroinflammatory diseases and find clues about their underlying pathophysiological mechanisms.

Domaines

Médecine humaine et pathologie

Camille Dubernet  : Connectez-vous pour contacter le contributeur

https://hal.science/hal-04732129

Soumis le : vendredi 11 octobre 2024-12:02:25

Dernière modification le : vendredi 15 novembre 2024-06:42:08

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Dates et versions

hal-04732129 , version 1 (11-10-2024)

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  • HAL Id : hal-04732129 , version 1

Citer

Nicolas Vince, Irène Charles, Sonia Bourguiba-Hachemi, Sandra Vukusic, Lakhdar Banyahya, et al.. Identification of new NMOSD and MOGAD genetic associations. 9th Joint ECTRIMS-ACTRIMS meeting, Oct 2023, Milan, Italy. Sage Publications Ltd, Multiple Sclerosis Journal, 29 (3S), pp.P125, 2023. ⟨hal-04732129⟩

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