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....
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-02893-w |
| _version_ | 1818575662895595520 |
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| author | Eva Suarez-Pajes Claudio Díaz-García Héctor Rodríguez-Pérez Jose M. Lorenzo-Salazar Itahisa Marcelino-Rodríguez Almudena Corrales Xiuwen Zheng Ariel Callero Eva Perez-Rodriguez Jose C. Garcia-Robaina Rafaela González-Montelongo Carlos Flores Beatriz Guillen-Guio |
| author_facet | Eva Suarez-Pajes Claudio Díaz-García Héctor Rodríguez-Pérez Jose M. Lorenzo-Salazar Itahisa Marcelino-Rodríguez Almudena Corrales Xiuwen Zheng Ariel Callero Eva Perez-Rodriguez Jose C. Garcia-Robaina Rafaela González-Montelongo Carlos Flores Beatriz Guillen-Guio |
| author_sort | Eva Suarez-Pajes |
| collection | DOAJ |
| description | 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]). |
| first_indexed | 2024-12-15T00:43:56Z |
| format | Article |
| id | doaj.art-ed784de2a5304a789e3bd2fc583edee2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-15T00:43:56Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ed784de2a5304a789e3bd2fc583edee22022-12-21T22:41:36ZengNature PortfolioScientific Reports2045-23222021-12-0111111010.1038/s41598-021-02893-wTargeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern EuropeansEva Suarez-Pajes0Claudio Díaz-García1Héctor Rodríguez-Pérez2Jose M. Lorenzo-Salazar3Itahisa Marcelino-Rodríguez4Almudena Corrales5Xiuwen Zheng6Ariel Callero7Eva Perez-Rodriguez8Jose C. Garcia-Robaina9Rafaela González-Montelongo10Carlos Flores11Beatriz Guillen-Guio12Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La LagunaResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La LagunaResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La LagunaGenomics Division, Instituto Tecnológico Y de Energías Renovables (ITER)Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La LagunaResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La LagunaDepartment of Biostatistics, University of WashingtonAllergy Unit, Hospital Universitario N.S. de CandelariaAllergy Unit, Hospital Universitario N.S. de CandelariaAllergy Unit, Hospital Universitario N.S. de CandelariaGenomics Division, Instituto Tecnológico Y de Energías Renovables (ITER)Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La LagunaResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La LagunaAbstract 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]).https://doi.org/10.1038/s41598-021-02893-w |
| spellingShingle | Eva Suarez-Pajes Claudio Díaz-García Héctor Rodríguez-Pérez Jose M. Lorenzo-Salazar Itahisa Marcelino-Rodríguez Almudena Corrales Xiuwen Zheng Ariel Callero Eva Perez-Rodriguez Jose C. Garcia-Robaina Rafaela González-Montelongo Carlos Flores Beatriz Guillen-Guio Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-021-02893-w |
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