AI Article Synopsis
- Asthma is a chronic inflammatory disease of the airways, and while studies have looked at its genetic roots, the role of HLA alleles has been underexplored until now.
- This study focused on a large group of individuals of African ancestry to investigate associations between HLA alleles and asthma-related traits, using advanced computational techniques to analyze genetics.
- Although no direct association with asthma susceptibility was found, the study identified a specific HLA allele linked to higher total serum IgE levels, highlighting the potential of advanced computational methods in understanding complex genetic associations.
Article Abstract
Background: Asthma is a complex chronic inflammatory disease of the airways. Association studies between HLA and asthma were first reported in the 1970s, and yet, the precise role of HLA alleles in asthma is not fully understood. Numerous genome-wide association studies were recently conducted on asthma, but were always limited to simple genetic markers (single nucleotide polymorphisms) and not complex HLA gene polymorphisms (alleles/haplotypes), therefore not capturing the biological relevance of this complex locus for asthma pathogenesis.
Objective: To run the first HLA-centric association study with asthma and specific asthma-related phenotypes in a large cohort of African-ancestry individuals.
Methods: We collected high-density genomics data for the Consortium on Asthma among African-ancestry Populations in the Americas (N = 4993) participants. Using computer-intensive machine-learning attribute bagging methods to infer HLA alleles, and Easy-HLA to infer HLA 5-gene haplotypes, we conducted a high-throughput HLA-centric association study of asthma susceptibility and total serum IgE (tIgE) levels in subjects with and without asthma.
Results: Among the 1607 individuals with asthma, 972 had available tIgE levels, with a mean tIgE level of 198.7 IU/mL. We could not identify any association with asthma susceptibility. However, we showed that HLA-DRB1∗09:01 was associated with increased tIgE levels (P = 8.5 × 10; weighted effect size, 0.51 [0.15-0.87]).
Conclusions: We identified for the first time an HLA allele associated with tIgE levels in African-ancestry individuals with asthma. Our report emphasizes that by leveraging powerful computational machine-learning methods, specific/extreme phenotypes, and population diversity, we can explore HLA gene polymorphisms in depth and reveal the full extent of complex disease associations.
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| http://dx.doi.org/10.1016/j.jaci.2020.01.011 | DOI Listing |
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