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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Published inScientific reports Vol. 11; no. 1; pp. 23686 - 10
Main Authors 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
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 08.12.2021
Nature Publishing Group
Nature Portfolio
Subjects
631/208
631/208/205
692/699/1785/31
Adult
Alleles
Allergies
Asthma
Asthma - epidemiology
Asthma - etiology
Autoimmune diseases
Black People - genetics
Case-Control Studies
Disease Susceptibility
DQA1 protein
Female
Food allergies
Gene mapping
Genetic Predisposition to Disease
Genomic analysis
Genomics - methods
Haplotypes
Health risks
Histocompatibility antigen HLA
HLA Antigens - genetics
Humanities and Social Sciences
Humans
Male
Meta-analysis
Middle Aged
multidisciplinary
Odds Ratio
Phenotypes
Population Surveillance
Risk Assessment
Risk Factors
Science
Science (multidisciplinary)
Spain - epidemiology
White People - genetics
Young Adult
Spain
Online AccessGet full text
ISSN2045-2322
2045-2322
DOI10.1038/s41598-021-02893-w

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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]).
AbstractList 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]).
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]).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]).
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]).
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]).
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 , 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 , 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 , OR [95% CI] = 0.47 [0.29- 0.73]).
ArticleNumber 23686
Author Marcelino-Rodríguez, Itahisa
Suarez-Pajes, Eva
Rodríguez-Pérez, Héctor
Garcia-Robaina, Jose C.
Lorenzo-Salazar, Jose M.
Callero, Ariel
González-Montelongo, Rafaela
Zheng, Xiuwen
Perez-Rodriguez, Eva
Díaz-García, Claudio
Flores, Carlos
Corrales, Almudena
Guillen-Guio, Beatriz
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/34880287$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_1186_s12920_022_01268_y
crossref_primary_10_1016_j_jaci_2023_05_018
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Snippet Despite asthma has a considerable genetic component, an important proportion of genetic risks remain unknown, especially for non-European populations. Canary...
Abstract Despite asthma has a considerable genetic component, an important proportion of genetic risks remain unknown, especially for non-European populations....
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SubjectTerms 631/208
631/208/205
692/699/1785/31
Adult
Alleles
Allergies
Asthma
Asthma - epidemiology
Asthma - etiology
Autoimmune diseases
Black People - genetics
Case-Control Studies
Disease Susceptibility
DQA1 protein
Female
Food allergies
Gene mapping
Genetic Predisposition to Disease
Genomic analysis
Genomics - methods
Haplotypes
Health risks
Histocompatibility antigen HLA
HLA Antigens - genetics
Humanities and Social Sciences
Humans
Male
Meta-analysis
Middle Aged
multidisciplinary
Odds Ratio
Phenotypes
Population Surveillance
Risk Assessment
Risk Factors
Science
Science (multidisciplinary)
Spain - epidemiology
White People - genetics
Young Adult
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Title Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans
URI https://link.springer.com/article/10.1038/s41598-021-02893-w
https://www.ncbi.nlm.nih.gov/pubmed/34880287
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https://pubmed.ncbi.nlm.nih.gov/PMC8654850
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Volume 11
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