Association of HLA-DRB1?09:01 with tIgE levels among African-ancestry individuals with asthma - 22/07/20
CAAPA
Dara Torgerson, PhD o, Pierre-Antoine Gourraud, PhD, MPH a, ⁎![](/templates/common/images/mail.png)
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 × 10−4; 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.
Il testo completo di questo articolo è disponibile in PDF.Key words : Asthma, HLA, tIgE levels, atopy, CAAPA, imputation, admixture
Abbreviations used : CAAPA, GWAS, tIgE
Mappa
N.V. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement number 846520. Funding for this study was provided in part by the National Institutes of Health (grant nos. R01-HL129239 and R01HL104608 to K.C.B.). |
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Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 146 - N° 1
P. 147-155 - Luglio 2020 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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