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

被引：266

作者：

Hirota, Tomomitsu ^{[1
]}

Takahashi, Atsushi ^{[2
]}

Kubo, Michiaki ^{[3
]}

Tsunoda, Tatsuhiko ^{[4
]}

Tomita, Kaori ^{[1
]}

Doi, Satoru ^{[5
]}

Fujita, Kimie ^{[6
]}

Miyatake, Akihiko ^{[6
]}

Enomoto, Tadao ^{[7
]}

Miyagawa, Takehiko ^{[8
]}

Adachi, Mitsuru ^{[9
]}

Tanaka, Hiroshi ^{[10
]}

Niimi, Akio ^{[11
]}

Matsumoto, Hisako ^{[11
]}

Ito, Isao ^{[11
]}

Masuko, Hironori ^{[12
]}

Sakamoto, Tohru ^{[12
]}

Hizawa, Nobuyuki ^{[12
]}

Taniguchi, Masami ^{[13
]}

Lima, John J. ^{[14
,15
]}

Irvin, Charles G. ^{[16
]}

Peters, Stephen P. ^{[17
]}

Himes, Blanca E. ^{[18
,19
]}

Litonjua, Augusto A. ^{[18
,19
]}

Tantisira, Kelan G. ^{[18
,19
]}

Weiss, Scott T. ^{[18
,19
]}

Kamatani, Naoyuki ^{[20
]}

Nakamura, Yusuke ^{[21
]}

Tamari, Mayumi ^{[1
]}

机构：

[1] RIKEN, Lab Resp Dis, Ctr Genom Med, Kanagawa, Japan

[2] RIKEN, Lab Stat Anal, Ctr Genom Med, Tokyo, Japan

[3] RIKEN, Lab Genotyping Dev, Ctr Genom Med, Kanagawa, Japan

[4] RIKEN, Lab Med Informat, Ctr Genom Med, Kanagawa, Japan

[5] Osaka Prefectural Med Ctr Resp & Allerg Dis, Osaka, Japan

[6] Miyatake Asthma Clin, Osaka, Japan

[7] Nonprofit Org NPO Japan Hlth Promot Supporting Ne, Wakayama, Japan

[8] Miyagawa Clin, Gifu, Japan

[9] Showa Univ, Sch Med, Dept Internal Med 1, Shinagawa Ku, Tokyo 142, Japan

[10] Sapporo Med Univ, Sch Med, Dept Internal Med 3, Sapporo, Hokkaido, Japan

[11] Kyoto Univ, Grad Sch Med, Dept Resp Med, Kyoto, Japan

[12] Univ Tsukuba, Inst Clin Med, Div Resp Med, Tsukuba, Ibaraki 305, Japan

[13] Sagamihara Natl Hosp, Natl Clin Res Ctr, Natl Hosp Org, Kanagawa, Japan

[14] Nemours Childrens Clin, Ctr Clin Pediat Pharmacol, Jacksonville, FL USA

[15] Nemours Childrens Clin, Ctr Pharmacogenet, Jacksonville, FL USA

[16] Univ Vermont, Dept Physiol & Med, Vermont Lung Ctr, Burlington, VT USA

[17] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Sect Pulm Crit Care Allergy & Immunol Dis, Winston Salem, NC USA

[18] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA

[19] Harvard Univ, Sch Med, Boston, MA USA

[20] RIKEN, Lab Int Alliance, Ctr Genom Med, Kanagawa, Japan

[21] Univ Tokyo, Inst Med Sci, Mol Med Lab, Tokyo, Japan

来源：

NATURE GENETICS | 2011年 / 43卷 / 09期

基金：

美国国家卫生研究院;

关键词：

PROSTATE-CANCER; VARIANTS; EXPRESSION; IMMUNITY; LINKAGE; TRAITS; GENES; CELLS; RISK; LUNG;

D O I：

10.1038/ng.887

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors(1,2). 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 x 10(-12)), a locus on chromosome 10p14 (P = 1.79 x 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 x 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 x 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.

引用

页码：893 / U108

页数：5

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