Scientific Reports (Aug 2020)
Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population
- Sandra Romero-Hidalgo,
- José Flores-Rivera,
- Verónica Rivas-Alonso,
- Rodrigo Barquera,
- María Teresa Villarreal-Molina,
- Bárbara Antuna-Puente,
- Luis Rodrigo Macias-Kauffer,
- Marisela Villalobos-Comparán,
- Jair Ortiz-Maldonado,
- Neng Yu,
- Tatiana V. Lebedeva,
- Sharon M. Alosco,
- Juan Daniel García-Rodríguez,
- Carolina González-Torres,
- Sandra Rosas-Madrigal,
- Graciela Ordoñez,
- Jorge Luis Guerrero-Camacho,
- Irene Treviño-Frenk,
- Monica Escamilla-Tilch,
- Maricela García-Lechuga,
- Víctor Hugo Tovar-Méndez,
- Hanna Pacheco-Ubaldo,
- Victor Acuña-Alonzo,
- Maria-Cátira Bortolini,
- Carla Gallo,
- Gabriel Bedoya,
- Francisco Rothhammer,
- Rolando González-Jose,
- Andrés Ruiz-Linares,
- Samuel Canizales-Quinteros,
- Edmond Yunis,
- Julio Granados,
- Teresa Corona
Affiliations
- Sandra Romero-Hidalgo
- Departamento de Genómica Computacional, Instituto Nacional de Medicina Genómica (INMEGEN)
- José Flores-Rivera
- Laboratorio Clínico de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez” (INNN)
- Verónica Rivas-Alonso
- Laboratorio Clínico de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez” (INNN)
- Rodrigo Barquera
- Molecular Genetics Laboratory, National School of Anthropology and History
- María Teresa Villarreal-Molina
- Laboratorio de Enfermedades Cardiovasculares, INMEGEN
- Bárbara Antuna-Puente
- Laboratorio de Enfermedades Cardiovasculares, INMEGEN
- Luis Rodrigo Macias-Kauffer
- Unidad de Genómica de Poblaciones Aplicada a La Salud, Facultad de Química, UNAM/INMEGEN
- Marisela Villalobos-Comparán
- Departamento de Genómica Computacional, Instituto Nacional de Medicina Genómica (INMEGEN)
- Jair Ortiz-Maldonado
- Laboratorio Clínico de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez” (INNN)
- Neng Yu
- HLA Laboratory, The American Red Cross Northeast Division
- Tatiana V. Lebedeva
- HLA Laboratory, The American Red Cross Northeast Division
- Sharon M. Alosco
- HLA Laboratory, The American Red Cross Northeast Division
- Juan Daniel García-Rodríguez
- Departamento de Genómica Computacional, Instituto Nacional de Medicina Genómica (INMEGEN)
- Carolina González-Torres
- Unidad de Secuenciación e Identificación de Polimorfismos, INMEGEN
- Sandra Rosas-Madrigal
- Laboratorio de Enfermedades Cardiovasculares, INMEGEN
- Graciela Ordoñez
- Neuroimmunology, INNN
- Jorge Luis Guerrero-Camacho
- Neurogenetics Department, INNN
- Irene Treviño-Frenk
- Department of Neurology, Instituto Nacional de Ciencias Medicas y Nutrición “Salvador Zubirán” (INCMNSZ)
- Monica Escamilla-Tilch
- Department of Transplantation, INCMNSZ
- Maricela García-Lechuga
- Department of Transplantation, INCMNSZ
- Víctor Hugo Tovar-Méndez
- Department of Transplantation, INCMNSZ
- Hanna Pacheco-Ubaldo
- Molecular Genetics Laboratory, National School of Anthropology and History
- Victor Acuña-Alonzo
- Molecular Genetics Laboratory, National School of Anthropology and History
- Maria-Cátira Bortolini
- Departamento de Genética, Universidade Federal Do Rio Grande Do Sul
- Carla Gallo
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia
- Gabriel Bedoya
- GENMOL (Genetica Molecular), Universidad de Antioquia
- Francisco Rothhammer
- Departamento de Tecnología Médica, Facultad de Ciencias de La Salud, Universidad de Tarapaca
- Rolando González-Jose
- Centro Nacional Patagónico, CONICET, Unidad de Diversidad, Sistematica Y Evolucion
- Andrés Ruiz-Linares
- Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London
- Samuel Canizales-Quinteros
- Unidad de Genómica de Poblaciones Aplicada a La Salud, Facultad de Química, UNAM/INMEGEN
- Edmond Yunis
- Department of Cancer Immunology and Virology, Dana Farber Cancer Institute
- Julio Granados
- Department of Transplantation, INCMNSZ
- Teresa Corona
- Laboratorio Clínico de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez” (INNN)
- DOI
- https://doi.org/10.1038/s41598-020-69224-3
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 11
Abstract
Abstract Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10–6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10–10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.
