@article{f9b5d4be8fbf46fdae53734fbc2b2ae9,
title = "Association of HLA-DRB1∗09:01 with tIgE levels among African-ancestry individuals with asthma",
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.",
keywords = "Asthma, CAAPA, HLA, admixture, atopy, imputation, tIgE levels",
author = "CAAPA and Nicolas Vince and Sophie Limou and Michelle Daya and Wataru Morii and Nicholas Rafaels and Estelle Geffard and Venceslas Douillard and Alexandre Walencik and Boorgula, {Meher Preethi} and Sameer Chavan and Candelaria Vergara and Ortega, {Victor E.} and Wilson, {James G.} and Lange, {Leslie A.} and Harold Watson and Nicolae, {Dan L.} and Meyers, {Deborah A.} and Hansel, {Nadia N.} and Ford, {Jean G.} and Faruque, {Mezbah U.} and Bleecker, {Eugene R.} and Monica Campbell and Beaty, {Terri H.} and Ingo Ruczinski and Mathias, {Rasika A.} and Taub, {Margaret A.} and Carole Ober and Emiko Noguchi and Barnes, {Kathleen C.} and Dara Torgerson and Gourraud, {Pierre Antoine}",
note = "Funding Information: We thank Labex IGO (ANR-11-LABX-0016-01) and IHU-CESTI for their support. We gratefully acknowledge the contributions of Pissamai and Trevor Maul, Paul Levett, Anselm Hennis, P. Michele Lashley, Raana Naidu, Malcolm Howitt, and Timothy Roach (BAGS), Audrey Grant, Eduardo Viera Ponte, Alvaro A. Cruz, and Edgar Carvalho (BIAS), Susan Balcer-Whaley, Maria Stockton-Porter, and Mao Yang (GRAAD), Delmy-Aracely Mej{\'i}a-Mej{\'i}a, Mario Meraz, Jaime Nu{\~n}ez, and Eileen Fabiani Herrera Mej{\'i}a (HONDAS), Trevor Ferguson and Deanna Ashley (JAAS), Silvia Jimenez, Nathalie Acevedo, and Dilia Mercado (PGCA), Ann Jedlicka (REACH), Addison K. May, Caroline Gilmore, and Patricia Minton (Vanderbilt University), Qun Niu (University of Chicago), and Adeyinka Falusi and Abayomi Odetunde (University of Ibadan, Nigeria). We also acknowledge the support of John Jay Shannon (Cook County Health Systems) and Kevin Weiss (Northwestern University), Regina Miranda and the Indians Zenues guards (San Basilio de Palenque, Bolivar, Colombia), Ulysse Ateba Ngoa (Leiden University), and Charles Rotimi, Adeyemo Adebowale, Floyd J. Malveaux, and Elena Reece (Howard University). We thank the numerous health care providers and community clinics and coinvestigators who assisted in the phenotyping and collection of DNA samples, and the families and patients for generously donating DNA samples to BAGS, BIAS, BREATHE, CAG, GRAAD, HONDAS, Jackson Heart Study, REACH, VALID, SARP, COPDGene, JAAS, PGCA, AEGS, and the asthma studies in Gabon and Palenque, Colombia. Special thanks to community leaders, teachers, doctors, and personnel from health centers at the Garifuna communities for organizing the medical brigades and to the medical students at Universidad Cat{\'o}lica de Honduras, Campus San Pedro y San Pablo for their participation in the fieldwork related to HONDAS; study coordinator Sandra Salazar; and health liaisons and public health officers of the main Conde office, Adaliudes Concei{\c c}{\~a}o, Luciana Quintela, Ivanice Santos, Anal{\'u} Lima, Benivaldo Valber Oliveira Silva, and Iraci Santos Araujo, and students from the Federal University of Bahia who assisted in data collection in BIAS: Rafael Santana, Roberta Barbosa, Ana Paula Santana, Charlton Barros, Marcele Brand{\~a}o, Ludmila Almeida, Thiago Cardoso, and Daniela Costa. We are grateful for the support from the international state governments and universities from Honduras, Colombia, Brazil, Gabon, Nigeria, the Netherlands, Jamaica, Barbados, and the United States who made this work possible. Funding Information: N.V. has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sk?odowska-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.). Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = jul,
doi = "10.1016/j.jaci.2020.01.011",
language = "English (US)",
volume = "146",
pages = "147--155",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "1",
}