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Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population.

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.

SUBMITTER: Romero-Hidalgo S

PROVIDER: S-EPMC7426416 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population.

Romero-Hidalgo Sandra S Flores-Rivera José J Rivas-Alonso Verónica V Barquera Rodrigo R Villarreal-Molina María Teresa MT Antuna-Puente Bárbara B Macias-Kauffer Luis Rodrigo LR Villalobos-Comparán Marisela M Ortiz-Maldonado Jair J Yu Neng N Lebedeva Tatiana V TV Alosco Sharon M SM García-Rodríguez Juan Daniel JD González-Torres Carolina C Rosas-Madrigal Sandra S Ordoñez Graciela G Guerrero-Camacho Jorge Luis JL Treviño-Frenk Irene I Escamilla-Tilch Monica M García-Lechuga Maricela M Tovar-Méndez Víctor Hugo VH Pacheco-Ubaldo Hanna H Acuña-Alonzo Victor V Bortolini Maria-Cátira MC Gallo Carla C Bedoya Gabriel G Rothhammer Francisco F González-Jose Rolando R Ruiz-Linares Andrés A Canizales-Quinteros Samuel S Yunis Edmond E Granados Julio J Corona Teresa T

Scientific reports 20200813 1

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 ...[more]

PMID: 32792643

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Project description:BackgroundLatin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk.Methods and study populationWe used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses.ResultsThe proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970-0.978, p = 3.1 × 10-40). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987-0.990, p = 1.4 × 10-44). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952-0.964; Mexican women: OR = 0.973, 95% CI 0.969-0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC.ConclusionsThe present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies.

Dataset Information

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population.

Publications

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population.

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