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

Tomomitsu Hirota; Atsushi Takahashi; Michiaki Kubo; Tatsuhiko Tsunoda; Kaori Tomita; Masafumi Sakashita; Takechiyo Yamada; Shigeharu Fujieda; Shota Tanaka; Satoru Doi; Akihiko Miyatake; Tadao Enomoto; Chiharu Nishiyama; Nobuhiro Nakano; Keiko Maeda; Ko Okumura; Hideoki Ogawa; Shigaku Ikeda; Emiko Noguchi; Tohru Sakamoto; Nobuyuki Hizawa; Koji Ebe; Hidehisa Saeki; Takashi Sasaki; Tamotsu Ebihara; Masayuki Amagai; Satoshi Takeuchi; Masutaka Furue; Yusuke Nakamura; Mayumi Tamari

doi:10.1038/ng.2438

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

Tomomitsu Hirota, Atsushi Takahashi, Michiaki Kubo, Tatsuhiko Tsunoda, Kaori Tomita, Masafumi Sakashita, Takechiyo Yamada, Shigeharu Fujieda, Shota Tanaka, Satoru Doi, Akihiko Miyatake, Tadao Enomoto, Chiharu Nishiyama, Nobuhiro Nakano, Keiko Maeda, Ko Okumura, Hideoki Ogawa, Shigaku Ikeda, Emiko Noguchi, Tohru SakamotoNobuyuki Hizawa, Koji Ebe, Hidehisa Saeki, Takashi Sasaki, Tamotsu Ebihara, Masayuki Amagai, Satoshi Takeuchi, Masutaka Furue, Yusuke Nakamura, Mayumi Tamari

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Abstract

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 × 10^-18), the major histocompatibility complex (MHC) region (P = 8.38 × 10^-20), OR10A3-NLRP10 (P = 1.54 × 10^-22), GLB1 (P = 2.77 × 10^-16), CCDC80 (P = 1.56 × 10^-19), CARD11 (P = 7.83 × 10^-9), ZNF365 (P = 5.85 × 10^-20) and CYP24A1-PFDN4 (P = 1.65 × 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.

Original language	English
Pages (from-to)	1222-1226
Number of pages	5
Journal	Nature Genetics
Volume	44
Issue number	11
DOIs	https://doi.org/10.1038/ng.2438
Publication status	Published - 11-2012

All Science Journal Classification (ASJC) codes

Genetics

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Hirota, T., Takahashi, A., Kubo, M., Tsunoda, T., Tomita, K., Sakashita, M., Yamada, T., Fujieda, S., Tanaka, S., Doi, S., Miyatake, A., Enomoto, T., Nishiyama, C., Nakano, N., Maeda, K., Okumura, K., Ogawa, H., Ikeda, S., Noguchi, E., ... Tamari, M. (2012). Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nature Genetics, 44(11), 1222-1226. https://doi.org/10.1038/ng.2438

Hirota, Tomomitsu ; Takahashi, Atsushi ; Kubo, Michiaki ; Tsunoda, Tatsuhiko ; Tomita, Kaori ; Sakashita, Masafumi ; Yamada, Takechiyo ; Fujieda, Shigeharu ; Tanaka, Shota ; Doi, Satoru ; Miyatake, Akihiko ; Enomoto, Tadao ; Nishiyama, Chiharu ; Nakano, Nobuhiro ; Maeda, Keiko ; Okumura, Ko ; Ogawa, Hideoki ; Ikeda, Shigaku ; Noguchi, Emiko ; Sakamoto, Tohru ; Hizawa, Nobuyuki ; Ebe, Koji ; Saeki, Hidehisa ; Sasaki, Takashi ; Ebihara, Tamotsu ; Amagai, Masayuki ; Takeuchi, Satoshi ; Furue, Masutaka ; Nakamura, Yusuke ; Tamari, Mayumi. / Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. In: Nature Genetics. 2012 ; Vol. 44, No. 11. pp. 1222-1226.

@article{f1abe16857af47c5a9f13dcf9f373cfd,

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

abstract = "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 × 10-18), the major histocompatibility complex (MHC) region (P = 8.38 × 10-20), OR10A3-NLRP10 (P = 1.54 × 10-22), GLB1 (P = 2.77 × 10-16), CCDC80 (P = 1.56 × 10-19), CARD11 (P = 7.83 × 10-9), ZNF365 (P = 5.85 × 10-20) and CYP24A1-PFDN4 (P = 1.65 × 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.",

author = "Tomomitsu Hirota and Atsushi Takahashi and Michiaki Kubo and Tatsuhiko Tsunoda and Kaori Tomita and Masafumi Sakashita and Takechiyo Yamada and Shigeharu Fujieda and Shota Tanaka and Satoru Doi and Akihiko Miyatake and Tadao Enomoto and Chiharu Nishiyama and Nobuhiro Nakano and Keiko Maeda and Ko Okumura and Hideoki Ogawa and Shigaku Ikeda and Emiko Noguchi and Tohru Sakamoto and Nobuyuki Hizawa and Koji Ebe and Hidehisa Saeki and Takashi Sasaki and Tamotsu Ebihara and Masayuki Amagai and Satoshi Takeuchi and Masutaka Furue and Yusuke Nakamura and Mayumi Tamari",

note = "Funding Information: We thank all the individuals who participated 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 and K. Barrymore for proofreading this manuscript. This work was conducted as part of the BioBank Japan Project, which is supported by the 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.",

year = "2012",

month = nov,

doi = "10.1038/ng.2438",

language = "English",

volume = "44",

pages = "1222--1226",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

}

Hirota, T, Takahashi, A, Kubo, M, Tsunoda, T, Tomita, K, Sakashita, M, Yamada, T, Fujieda, S, Tanaka, S, Doi, S, Miyatake, A, Enomoto, T, Nishiyama, C, Nakano, N, Maeda, K, Okumura, K, Ogawa, H, Ikeda, S, Noguchi, E, Sakamoto, T, Hizawa, N, Ebe, K, Saeki, H, Sasaki, T, Ebihara, T, Amagai, M, Takeuchi, S, Furue, M, Nakamura, Y & Tamari, M 2012, 'Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population', Nature Genetics, vol. 44, no. 11, pp. 1222-1226. https://doi.org/10.1038/ng.2438

Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. / Hirota, Tomomitsu; Takahashi, Atsushi; Kubo, Michiaki; Tsunoda, Tatsuhiko; Tomita, Kaori; Sakashita, Masafumi; Yamada, Takechiyo; Fujieda, Shigeharu; Tanaka, Shota; Doi, Satoru; Miyatake, Akihiko; Enomoto, Tadao; Nishiyama, Chiharu; Nakano, Nobuhiro; Maeda, Keiko; Okumura, Ko; Ogawa, Hideoki; Ikeda, Shigaku; Noguchi, Emiko; Sakamoto, Tohru; Hizawa, Nobuyuki; Ebe, Koji; Saeki, Hidehisa; Sasaki, Takashi; Ebihara, Tamotsu; Amagai, Masayuki; Takeuchi, Satoshi; Furue, Masutaka; Nakamura, Yusuke; Tamari, Mayumi.

In: Nature Genetics, Vol. 44, No. 11, 11.2012, p. 1222-1226.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population

AU - Hirota, Tomomitsu

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Tsunoda, Tatsuhiko

AU - Tomita, Kaori

AU - Sakashita, Masafumi

AU - Yamada, Takechiyo

AU - Fujieda, Shigeharu

AU - Tanaka, Shota

AU - Doi, Satoru

AU - Miyatake, Akihiko

AU - Enomoto, Tadao

AU - Nishiyama, Chiharu

AU - Nakano, Nobuhiro

AU - Maeda, Keiko

AU - Okumura, Ko

AU - Ogawa, Hideoki

AU - Ikeda, Shigaku

AU - Noguchi, Emiko

AU - Sakamoto, Tohru

AU - Hizawa, Nobuyuki

AU - Ebe, Koji

AU - Saeki, Hidehisa

AU - Sasaki, Takashi

AU - Ebihara, Tamotsu

AU - Amagai, Masayuki

AU - Takeuchi, Satoshi

AU - Furue, Masutaka

AU - Nakamura, Yusuke

AU - Tamari, Mayumi

N1 - Funding Information: We thank all the individuals who participated 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 and K. Barrymore for proofreading this manuscript. This work was conducted as part of the BioBank Japan Project, which is supported by the 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.

PY - 2012/11

Y1 - 2012/11

N2 - 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 × 10-18), the major histocompatibility complex (MHC) region (P = 8.38 × 10-20), OR10A3-NLRP10 (P = 1.54 × 10-22), GLB1 (P = 2.77 × 10-16), CCDC80 (P = 1.56 × 10-19), CARD11 (P = 7.83 × 10-9), ZNF365 (P = 5.85 × 10-20) and CYP24A1-PFDN4 (P = 1.65 × 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.

AB - 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 × 10-18), the major histocompatibility complex (MHC) region (P = 8.38 × 10-20), OR10A3-NLRP10 (P = 1.54 × 10-22), GLB1 (P = 2.77 × 10-16), CCDC80 (P = 1.56 × 10-19), CARD11 (P = 7.83 × 10-9), ZNF365 (P = 5.85 × 10-20) and CYP24A1-PFDN4 (P = 1.65 × 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.

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SN - 1061-4036

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ER -

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

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