Title

Association of HLA-DRB1∗09:01 with tIgE levels among African-ancestry individuals with asthma

Authors

Nicolas Vince, Université de Nantes
Sophie Limou, Université de Nantes
Michelle Daya, University of Colorado Anschutz Medical Campus
Wataru Morii, University of Tsukuba
Nicholas Rafaels, University of Colorado Anschutz Medical Campus
Estelle Geffard, Université de Nantes
Venceslas Douillard, Université de Nantes
Alexandre Walencik, Université de Nantes
Meher Preethi Boorgula, University of Colorado Anschutz Medical Campus
Sameer Chavan, University of Colorado Anschutz Medical Campus
Candelaria Vergara, Johns Hopkins University
Victor E. Ortega, Wake Forest School of Medicine
James G. Wilson, University of Mississippi Medical Center
Leslie A. Lange, University of Colorado Anschutz Medical Campus
Harold Watson, The University of the West Indies
Dan L. Nicolae, The University of Chicago
Deborah A. Meyers, University of Arizona College of Medicine – Tucson
Nadia N. Hansel, Johns Hopkins University
Jean G. Ford, Albert Einstein Healthcare Network
Mezbah U. Faruque, Howard University College of Medicine
Eugene R. Bleecker, University of Arizona College of Medicine – Tucson
Monica Campbell, University of Colorado Anschutz Medical Campus
Terri H. Beaty, Johns Hopkins Bloomberg School of Public Health
Ingo Ruczinski, Johns Hopkins Bloomberg School of Public Health
Rasika A. Mathias, Johns Hopkins University
Margaret A. Taub, Johns Hopkins Bloomberg School of Public Health
Carole Ober, The University of Chicago
Emiko Noguchi, University of Tsukuba
Kathleen C. Barnes, University of Colorado Anschutz Medical Campus
Dara Torgerson, Université McGill
Pierre Antoine Gourraud, Université de Nantes

Document Type

Article

Publication Date

7-1-2020

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.

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