J Allergy Clin Immunol. 2021 Mar 10:S0091-6749(21)00366-3. doi: 10.1016/j.jaci.2021.02.035. Online ahead of print.
BACKGROUND: Genetic ancestry plays a role in asthma health disparities.
OBJECTIVE: To evaluate the impact of ancestry on, and identify genetic variants associated with asthma, serum immunoglobulin E (IgE), and lung function.
METHODS: 436 Peruvian children (9-19 years) with asthma and 291 without asthma were genotyped using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of Indigenous ancestry from continental America (NAT) and European ancestry from Iberian Populations in Spain (IBS) were estimated using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes, and performed a genome-wide association study.
RESULTS: Mean ancestry was 84.7% NAT (cases: 84.2%; controls: 85.4%) and 15.3% IBS (15.8%; 14.6%). Adjusting for asthma, NAT was associated with higher IgE (p<0.001) and IBS with lower IgE levels (p<0.001). NAT was associated with higher FEV1 percent-predicted (p=0.001) while IBS was associated with lower FEV1 in the controls but not cases. The HLA-DR/DQ region on chromosome 6 was strongly associated with IgE (rs3135348, p =3.438×10-10), and is independent of an association with the haplotype HLA-DQA1∼HLA-DQB1:04.01∼04.02 (p = 1.55×10-05). For lung function, we identified a locus (rs4410198, p = 5.536×10-11) mapping to chromosome 19, near a cluster of zinc finger interacting genes that co-localizes to the LncRNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric asthma cases with similar admixture from Brazil (p = 0.005).
CONCLUSION: This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a LncRNA for lung function that may be specific to children with Indigenous ancestry from continental America.