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

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...

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Autores principales: Suarez-Pajes, Eva, Díaz-García, Claudio, Rodríguez-Pérez, Héctor, Lorenzo-Salazar, Jose M., Marcelino-Rodríguez, Itahisa, Corrales, Almudena, Zheng, Xiuwen, Callero, Ariel, Perez-Rodriguez, Eva, Garcia-Robaina, Jose C., González-Montelongo, Rafaela, Flores, Carlos, Guillen-Guio, Beatriz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654850/
https://www.ncbi.nlm.nih.gov/pubmed/34880287
http://dx.doi.org/10.1038/s41598-021-02893-w
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author Suarez-Pajes, Eva
Díaz-García, Claudio
Rodríguez-Pérez, Héctor
Lorenzo-Salazar, Jose M.
Marcelino-Rodríguez, Itahisa
Corrales, Almudena
Zheng, Xiuwen
Callero, Ariel
Perez-Rodriguez, Eva
Garcia-Robaina, Jose C.
González-Montelongo, Rafaela
Flores, Carlos
Guillen-Guio, Beatriz
author_facet Suarez-Pajes, Eva
Díaz-García, Claudio
Rodríguez-Pérez, Héctor
Lorenzo-Salazar, Jose M.
Marcelino-Rodríguez, Itahisa
Corrales, Almudena
Zheng, Xiuwen
Callero, Ariel
Perez-Rodriguez, Eva
Garcia-Robaina, Jose C.
González-Montelongo, Rafaela
Flores, Carlos
Guillen-Guio, Beatriz
author_sort Suarez-Pajes, Eva
collection PubMed
description 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]).
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spelling pubmed-86548502021-12-09 Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans Suarez-Pajes, Eva Díaz-García, Claudio Rodríguez-Pérez, Héctor Lorenzo-Salazar, Jose M. Marcelino-Rodríguez, Itahisa Corrales, Almudena Zheng, Xiuwen Callero, Ariel Perez-Rodriguez, Eva Garcia-Robaina, Jose C. González-Montelongo, Rafaela Flores, Carlos Guillen-Guio, Beatriz Sci Rep Article 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]). Nature Publishing Group UK 2021-12-08 /pmc/articles/PMC8654850/ /pubmed/34880287 http://dx.doi.org/10.1038/s41598-021-02893-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Suarez-Pajes, Eva
Díaz-García, Claudio
Rodríguez-Pérez, Héctor
Lorenzo-Salazar, Jose M.
Marcelino-Rodríguez, Itahisa
Corrales, Almudena
Zheng, Xiuwen
Callero, Ariel
Perez-Rodriguez, Eva
Garcia-Robaina, Jose C.
González-Montelongo, Rafaela
Flores, Carlos
Guillen-Guio, Beatriz
Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans
title Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans
title_full Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans
title_fullStr Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans
title_full_unstemmed Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans
title_short Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans
title_sort targeted analysis of genomic regions enriched in african ancestry reveals novel classical hla alleles associated with asthma in southwestern europeans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654850/
https://www.ncbi.nlm.nih.gov/pubmed/34880287
http://dx.doi.org/10.1038/s41598-021-02893-w
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