Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population

Tomomitsu Hirota; Atsushi Takahashi; Michiaki Kubo; Tatsuhiko Tsunoda; Kaori Tomita; Satoru Doi; Kimie Fujita; Akihiko Miyatake; Tadao Enomoto; Takehiko Miyagawa; Mitsuru Adachi; Hiroshi Tanaka; Akio Niimi; Hisako Matsumoto; Isao Ito; Hironori Masuko; Tohru Sakamoto; Nobuyuki Hizawa; Masami Taniguchi; John J. Lima; Charles G. Irvin; Stephen P. Peters; Blanca E. Himes; Augusto A. Litonjua; Kelan G. Tantisira; Scott T. Weiss; Naoyuki Kamatani; Yusuke Nakamura; Mayumi Tamari

doi:10.1038/ng.887

Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population

Tomomitsu Hirota, Atsushi Takahashi, Michiaki Kubo, Tatsuhiko Tsunoda, Kaori Tomita, Satoru Doi, Kimie Fujita, Akihiko Miyatake, Tadao Enomoto, Takehiko Miyagawa, Mitsuru Adachi, Hiroshi Tanaka, Akio Niimi, Hisako Matsumoto, Isao Ito, Hironori Masuko, Tohru Sakamoto, Nobuyuki Hizawa, Masami Taniguchi, John J. LimaCharles G. Irvin, Stephen P. Peters, Blanca E. Himes, Augusto A. Litonjua, Kelan G. Tantisira, Scott T. Weiss, Naoyuki Kamatani, Yusuke Nakamura, Mayumi Tamari

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Abstract

Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. 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 FEV 1/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.

Original language	English
Pages (from-to)	893-896
Number of pages	4
Journal	Nature Genetics
Volume	43
Issue number	9
DOIs	https://doi.org/10.1038/ng.887
Publication status	Published - 09-2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics

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Hirota, T., Takahashi, A., Kubo, M., Tsunoda, T., Tomita, K., Doi, S., Fujita, K., Miyatake, A., Enomoto, T., Miyagawa, T., Adachi, M., Tanaka, H., Niimi, A., Matsumoto, H., Ito, I., Masuko, H., Sakamoto, T., Hizawa, N., Taniguchi, M., ... Tamari, M. (2011). Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nature Genetics, 43(9), 893-896. https://doi.org/10.1038/ng.887

@article{d2e56a7e4fb84b44a00146ef565625bb,

title = "Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population",

abstract = "Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. 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 FEV 1/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.",

author = "Tomomitsu Hirota and Atsushi Takahashi and Michiaki Kubo and Tatsuhiko Tsunoda and Kaori Tomita and Satoru Doi and Kimie Fujita and Akihiko Miyatake and Tadao Enomoto and Takehiko Miyagawa and Mitsuru Adachi and Hiroshi Tanaka and Akio Niimi and Hisako Matsumoto and Isao Ito and Hironori Masuko and Tohru Sakamoto and Nobuyuki Hizawa and Masami Taniguchi and Lima, {John J.} and Irvin, {Charles G.} and Peters, {Stephen P.} and Himes, {Blanca E.} and Litonjua, {Augusto A.} and Tantisira, {Kelan G.} and Weiss, {Scott T.} and Naoyuki Kamatani and Yusuke Nakamura and Mayumi Tamari",

note = "Funding Information: 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{\textquoteright}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{\textquoteright}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.",

year = "2011",

month = sep,

doi = "10.1038/ng.887",

language = "English",

volume = "43",

pages = "893--896",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

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Hirota, T, Takahashi, A, Kubo, M, Tsunoda, T, Tomita, K, Doi, S, Fujita, K, Miyatake, A, Enomoto, T, Miyagawa, T, Adachi, M, Tanaka, H, Niimi, A, Matsumoto, H, Ito, I, Masuko, H, Sakamoto, T, Hizawa, N, Taniguchi, M, Lima, JJ, Irvin, CG, Peters, SP, Himes, BE, Litonjua, AA, Tantisira, KG, Weiss, ST, Kamatani, N, Nakamura, Y & Tamari, M 2011, 'Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population', Nature Genetics, vol. 43, no. 9, pp. 893-896. https://doi.org/10.1038/ng.887

TY - JOUR

T1 - Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population

AU - Hirota, Tomomitsu

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Tsunoda, Tatsuhiko

AU - Tomita, Kaori

AU - Doi, Satoru

AU - Fujita, Kimie

AU - Miyatake, Akihiko

AU - Enomoto, Tadao

AU - Miyagawa, Takehiko

AU - Adachi, Mitsuru

AU - Tanaka, Hiroshi

AU - Niimi, Akio

AU - Matsumoto, Hisako

AU - Ito, Isao

AU - Masuko, Hironori

AU - Sakamoto, Tohru

AU - Hizawa, Nobuyuki

AU - Taniguchi, Masami

AU - Lima, John J.

AU - Irvin, Charles G.

AU - Peters, Stephen P.

AU - Himes, Blanca E.

AU - Litonjua, Augusto A.

AU - Tantisira, Kelan G.

AU - Weiss, Scott T.

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Tamari, Mayumi

N1 - Funding Information: 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.

PY - 2011/9

Y1 - 2011/9

N2 - Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. 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 FEV 1/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.

AB - Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. 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 FEV 1/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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Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population

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