TY - JOUR
T1 - Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population
AU - Romero-Hidalgo, Sandra
AU - Flores-Rivera, José
AU - Rivas-Alonso, Verónica
AU - Barquera, Rodrigo
AU - Villarreal-Molina, María Teresa
AU - Antuna-Puente, Bárbara
AU - Macias-Kauffer, Luis Rodrigo
AU - Villalobos-Comparán, Marisela
AU - Ortiz-Maldonado, Jair
AU - Yu, Neng
AU - Lebedeva, Tatiana V.
AU - Alosco, Sharon M.
AU - García-Rodríguez, Juan Daniel
AU - González-Torres, Carolina
AU - Rosas-Madrigal, Sandra
AU - Ordoñez, Graciela
AU - Guerrero-Camacho, Jorge Luis
AU - Treviño-Frenk, Irene
AU - Escamilla-Tilch, Monica
AU - García-Lechuga, Maricela
AU - Tovar-Méndez, Víctor Hugo
AU - Pacheco-Ubaldo, Hanna
AU - Acuña-Alonzo, Victor
AU - Bortolini, Maria Cátira
AU - Gallo, Carla
AU - Bedoya, Gabriel
AU - Rothhammer, Francisco
AU - González-Jose, Rolando
AU - Ruiz-Linares, Andrés
AU - Canizales-Quinteros, Samuel
AU - Yunis, Edmond
AU - Granados, Julio
AU - Corona, Teresa
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85089366953
U2 - 10.1038/s41598-020-69224-3
DO - 10.1038/s41598-020-69224-3
M3 - Artículo
C2 - 32792643
AN - SCOPUS:85089366953
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 13706
ER -