Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors1,2. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10−12), a locus on chromosome 10p14 (P = 1.79 × 10−15) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10−13). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10−23), which is close to rs2070600, a SNP previously reported for association with FEV1/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.
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We thank all the subjects for participating in the study and also thank the collaborating physicians for helping with sample collection. We are grateful to the members of BioBank Japan and the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. We thank M.T. Shimizu, H. Sekiguchi, A.I. Jodo, N. Kawaraichi and the technical staff of the Center for Genomic Medicine for providing technical assistance. This work was conducted as a part of the BioBank Japan Project supported by of Ministry of Education, Culture, Sports, Science and Technology, Japan. This work was also partly supported by grants from the Ministry of Health, Labour and Welfare, Japan. We acknowledge the American Lung Association (ALA) and the ALA's Asthma Clinical Research Centers investigators and research teams for use of Leukotriene Modifier or Corticosteroid Salmeterol (LOCCS) and Effectiveness of Low Dose Theophylline as an Add-on Treatment in Asthma (LODO) data, with additional funding from HL071394 and HL074755 from the National Heart, Lung, and Blood Institute and the Nemours Children's Clinic. GlaxoSmithKline supported the conduct of the LOCCS Trial by an unrestricted grant to the ALA. We acknowledge Sepracor, Inc. for use of the Asthma Trial data. C.G.I. was supported by grants from the US National Institutes of Health NCRR RR022675 and RR015557 as well as the ALA, Asthma Clinical Research Center award. S.P.P. serves as an advisor to the data coordinating center of the ALA Asthma Clinical Research Centers and served as the principal investigator of the LOCCS trial.
The authors declare no competing financial interests.
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Hirota, T., Takahashi, A., Kubo, M. et al. Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat Genet 43, 893–896 (2011). https://doi.org/10.1038/ng.887
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