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

Nature Genetics volume 44, pages 1222–1226 (2012)Cite this article

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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 (Pcombined = 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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Figure 1: Manhattan plot showing the −log10P values of 606,164 SNPs in the GWAS for 1,472 Japanese atopic dermatitis cases and 7,971 controls plotted against their respective positions on autosomes and the X chromosome.
Figure 2: Regional plots of association results within eight newly identified susceptibility regions for atopic dermatitis.

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Acknowledgements

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.

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Authors and Affiliations

  1. Laboratory for Respiratory Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Japan

    Tomomitsu Hirota, Shota Tanaka & Mayumi Tamari

  2. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Minato-ku, Japan

    Atsushi Takahashi

  3. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Japan

    Michiaki Kubo

  4. Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Yokohama, Japan

    Tatsuhiko Tsunoda

  5. Department of Otorhinolaryngology, Fukui Medical University, Matsuoka, Japan

    Kaori Tomita, Masafumi Sakashita, Takechiyo Yamada & Shigeharu Fujieda

  6. Department of Otolaryngology–Head and Neck Surgery, University of Yamanashi, Faculty of Medicine, Chuo, Japan

    Shota Tanaka

  7. Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan

    Satoru Doi

  8. Miyatake Asthma Clinic, Osaka, Japan

    Akihiko Miyatake

  9. Nonprofit Organization (NPO) Japan Health Promotion Supporting Network, Wakayama, Japan

    Tadao Enomoto

  10. Atopy Research Center, Juntendo University School of Medicine, Bunkyo-ku, Japan

    Chiharu Nishiyama, Nobuhiro Nakano, Keiko Maeda, Ko Okumura & Hideoki Ogawa

  11. Department of Dermatology, Juntendo University School of Medicine, Bunkyo-ku, Japan

    Shigaku Ikeda

  12. Department of Medical Genetics, Majors of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

    Emiko Noguchi

  13. Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Saitama, Japan

    Emiko Noguchi

  14. Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan

    Tohru Sakamoto & Nobuyuki Hizawa

  15. Department of Dermatology, Takao Hospital, Kyoto, Japan

    Koji Ebe

  16. Department of Dermatology, Jikei University School of Medicine, Minato-ku, Japan

    Hidehisa Saeki

  17. Department of Dermatology, Keio University School of Medicine, Shinjuku-ku, Japan

    Takashi Sasaki, Tamotsu Ebihara & Masayuki Amagai

  18. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Satoshi Takeuchi & Masutaka Furue

  19. Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Japan

    Yusuke Nakamura

Authors
  1. Tomomitsu Hirota
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  2. Atsushi Takahashi
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Contributions

T.H. and M.T. designed the study and drafted the manuscript. A.T. and T.T. analyzed the GWAS data. T.H., K.T., S. Tanaka and M.K. performed the genotyping for the GWAS. M.S., T.Y., S.F., S.D., A.M., T. Enomoto, C.N., N.N., K.M., S.I., K.O., H.O., E.N., T. Sakamoto, N.H., K.E., H.S., T. Sasaki, T. Ebihara, M.A., S. Takeuchi and M.F. recruited subjects and participated in the diagnostic evaluations. M.T. wrote the manuscript. M.K. and Y.N. contributed to the overall GWAS study design.

Corresponding author

Correspondence to Mayumi Tamari.

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The authors declare no competing financial interests.

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Hirota, T., Takahashi, A., Kubo, M. et al. Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet 44, 1222–1226 (2012). https://doi.org/10.1038/ng.2438

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