Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population

被引：282

作者：

Hirota, Tomomitsu ^{[1
]}

Takahashi, Atsushi ^{[2
]}

Kubo, Michiaki ^{[3
]}

Tsunoda, Tatsuhiko ^{[4
]}

Tomita, Kaori ^{[5
]}

Sakashita, Masafumi ^{[5
]}

Yamada, Takechiyo ^{[5
]}

Fujieda, Shigeharu ^{[5
]}

Tanaka, Shota ^{[1
,6
]}

Doi, Satoru ^{[7
]}

Miyatake, Akihiko ^{[8
]}

Enomoto, Tadao ^{[9
]}

Nishiyama, Chiharu ^{[10
]}

Nakano, Nobuhiro ^{[10
]}

Maeda, Keiko ^{[10
]}

Okumura, Ko ^{[10
]}

Ogawa, Hideoki ^{[10
]}

Ikeda, Shigaku ^{[11
]}

Noguchi, Emiko ^{[12
,13
]}

Sakamoto, Tohru ^{[14
]}

Hizawa, Nobuyuki ^{[14
]}

Ebe, Koji ^{[16
]}

Saeki, Hidehisa ^{[15
]}

Sasaki, Takashi ^{[19
]}

Ebihara, Tamotsu ^{[19
]}

Amagai, Masayuki ^{[19
]}

Takeuchi, Satoshi ^{[17
]}

Furue, Masutaka ^{[17
]}

Nakamura, Yusuke ^{[18
]}

Tamari, Mayumi ^{[1
]}

机构：

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

[2] RIKEN, Ctr Genom Med, Lab Stat Anal, Minato Ku, Yokohama, Kanagawa, Japan

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

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

[5] Fukui Med Univ, Dept Otorhinolaryngol, Matsuoka, Fukui, Japan

[6] Univ Yamanashi, Fac Med, Dept Otolaryngol Head & Neck Surg, Chuo Ku, Tamaho, Yamanashi, Japan

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

[8] Miyatake Asthma Clin, Osaka, Japan

[9] Japan Hlth Promot Supporting Network, Nonprofit Org NPO, Wakayama, Japan

[10] Juntendo Univ, Sch Med, Atopy Res Ctr, Bunkyo Ku, Tokyo, Japan

[11] Juntendo Univ, Sch Med, Dept Dermatol, Bunkyo Ku, Tokyo, Japan

[12] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Med Genet, Tsukuba, Ibaraki, Japan

[13] Japan Sci & Technol Agcy, CREST, Saitama, Japan

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

[15] Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo, Japan

[16] Takao Hosp, Dept Dermatol, Kyoto, Japan

[17] Kyushu Univ, Grad Sch Med Sci, Dept Dermatol, Fukuoka 812, Japan

[18] Univ Tokyo, Inst Med Sci, Mol Med Lab, Minato Ku, Tokyo 1138654, Japan

[19] Keio Univ, Sch Med, Dept Dermatol, Shinjuku Ku, Tokyo 108, Japan

来源：

NATURE GENETICS | 2012年 / 44卷 / 11期

关键词：

DISEASE; KERATINOCYTES; METAANALYSIS; MODULATION; MECHANISMS; EXPRESSION; FILAGGRIN; VARIANTS; CARMA1; ASTHMA;

D O I：

10.1038/ng.2438

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Atopic dermatitis is a common inflammatory skin disease caused by interaction of genetic and environmental factors. On the basis of data from a genome-wide association study (GWAS) and a validation study comprising a total of 3,328 subjects with atopic dermatitis and 14,992 controls in the Japanese population, we report here 8 new susceptibility loci: IL1RL1-IL18R1-IL18RAP (P-combined = 8.36 x 10(-18)), the major histocompatibility complex (MHC) region (P = 8.38 x 10(-20)), OR10A3-NLRP10 (P = 1.54 x 10(-22)), GLB1 (P = 2.77 x 10(-16)), CCDC80 (P = 1.56 x 10(-19)), CARD11 (P = 7.83 x ZNF365 (P = 5.85 x 10(-20)) and CYP24A1-PFDN4 (P = 1.65 x 10(-8)). We also replicated the associations of the FLG, C11orf30, TMEM232-SLC25A46, TNFRSF6B-ZGPAT, OVOL1, ACTL9 and KIF3A-IL13 loci that were previously reported in GWAS of European and Chinese individuals and a meta-analysis of GWAS for atopic dermatitis. These findings advance the understanding of the genetic basis of atopic dermatitis.

引用

页码：1222 / 1226

页数：5

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