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Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans.

ABSTRACT: Despite asthma has a considerable genetic component, an important proportion of genetic risks remain unknown, especially for non-European populations. Canary Islanders have the largest African genetic ancestry observed among Southwestern Europeans and the highest asthma prevalence in Spain. Here we examined broad chromosomal regions previously associated with an excess of African genetic ancestry in Canary Islanders, with the aim of identifying novel risk variants associated with asthma susceptibility. In a two-stage cases-control study, we revealed a variant within HLA-DQB1 significantly associated with asthma risk (rs1049213, meta-analysis p = 1.30 × 10^-7, OR [95% CI] = 1.74 [1.41-2.13]) previously associated with asthma and broad allergic phenotype. Subsequent fine-mapping analyses of classical HLA alleles revealed a novel allele significantly associated with asthma protection (HLA-DQA1*01:02, meta-analysis p = 3.98 × 10^-4, OR [95% CI] = 0.64 [0.50-0.82]) that had been linked to infectious and autoimmune diseases, and peanut allergy. HLA haplotype analyses revealed a novel haplotype DQA1*01:02-DQB1*06:04 conferring asthma protection (meta-analysis p = 4.71 × 10^-4, OR [95% CI] = 0.47 [0.29- 0.73]).

SUBMITTER: Suarez-Pajes E

PROVIDER: S-EPMC8654850 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans.

Suarez-Pajes Eva E Díaz-García Claudio C Rodríguez-Pérez Héctor H Lorenzo-Salazar Jose M JM Marcelino-Rodríguez Itahisa I Corrales Almudena A Zheng Xiuwen X Callero Ariel A Perez-Rodriguez Eva E Garcia-Robaina Jose C JC González-Montelongo Rafaela R Flores Carlos C Guillen-Guio Beatriz B

Scientific reports 20211208 1

Despite asthma has a considerable genetic component, an important proportion of genetic risks remain unknown, especially for non-European populations. Canary Islanders have the largest African genetic ancestry observed among Southwestern Europeans and the highest asthma prevalence in Spain. Here we examined broad chromosomal regions previously associated with an excess of African genetic ancestry in Canary Islanders, with the aim of identifying novel risk variants associated with asthma suscepti ...[more]

PMID: 34880287

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Project description:BackgroundPersistent cervical high-risk human papillomavirus (hrHPV) infection is a necessary cause of cervical cancer. However, the host genetic factors underlying its risk are not well understood. We hypothesized that immunogenetic variation plays a role in hrHPV infection and persistence. Therefore, we conducted a study of classical HLA alleles and their association with hrHPV infection and persistence among women.MethodsWe characterized HPV infection using SPF10/LiPA25in Nigerian women at baseline and at 6 months follow-up visits in 2014. hrHPV infection was prevalent if at least one carcinogenic HPV genotype was detected at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected at the baseline and follow-up visits. Classical HLA alleles were imputed from genotypes in the MHC region using the HLA genotype imputation with attribute bagging (HIBAG) algorithm. HLA association tests were conducted under additive genetic models.ResultsThe mean (±SD) age of the 517 study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive at baseline and 10% had persistent hrHPV infections. In multivariate regression models adjusted for age, HIV status and the first principal component, DQA1*01:02 and DQA1*02:01 were positively associated with prevalent but not persistent hrHPV infections, while DQA1*05:01 was negatively associated with prevalent hrHPV but positively associated with persistent cervical hrHPV infections. Four haplotypes (A*30:01-DQA1*05:01, B*07:02-C*07:02, B*07:02-DQA1*05:01 and C*07:02-DQA1*05:01) were significantly associated with prevalent cervical hrHPV infections and several haplotypes that included the DQA1*05:01 allelic variant were significantly associated with persistent cervical hrHPV infections. Six amino acid positions on DQα1 were associated with prevalent but not persistent cervical hrHPV infections.ConclusionsIn this first study to investigate the association between HLA alleles and persistent hrHPV in African women, we identified important risk alleles that merit further investigation. Our findings provide new insights into risk factors for hrHPV infection in African ancestry women.

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Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans.

Publications

Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans.

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