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

• Published in: Scientific 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
• Language: English
• 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-02893-w

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]).