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Genetic Architectures Underlie Onset Age of Atopic Dermatitis

  • Keiko Hikino
    Affiliations
    Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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  • Nao Tanaka
    Affiliations
    Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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  • Masaru Koido
    Affiliations
    Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
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  • Kohei Tomizuka
    Affiliations
    Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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  • Yoshinao Koike
    Affiliations
    Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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  • Shuji Ito
    Affiliations
    Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Department of Orthopedic Surgery, Faculty of Medicine, Shimane University, Izumo, Japan
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  • Akari Suzuki
    Affiliations
    Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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  • Yukihide Momozawa
    Affiliations
    Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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  • Yoichiro Kamatani
    Affiliations
    Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
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  • Affiliations
    The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Taisei Mushiroda
    Affiliations
    Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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  • Chikashi Terao
    Correspondence
    Corresponding author
    Affiliations
    Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan

    Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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      Genetic attributions for age of onset have been investigated for multiple entities (
      • Blauwendraat C.
      • Heilbron K.
      • Vallerga C.L.
      • Bandres-Ciga S.
      • von Coelln R.
      • Pihlstrøm L.
      • et al.
      Parkinson's disease age at onset genome-wide association study: defining heritability, genetic loci, and alpha-synuclein mechanisms.
      ;
      • Kamboh M.I.
      • Barmada M.M.
      • Demirci F.Y.
      • Minster R.L.
      • Carrasquillo M.M.
      • Pankratz V.S.
      • et al.
      Genome-wide association analysis of age-at-onset in Alzheimer's disease.
      ;
      • Power R.A.
      • Tansey K.E.
      • Buttenschøn H.N.
      • Cohen-Woods S.
      • Bigdeli T.
      • Hall L.S.
      • et al.
      Genome-wide association for major depression through age at onset stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.
      ;
      • Woolston A.L.
      • Hsiao P.C.
      • Kuo P.H.
      • Wang S.H.
      • Lien Y.J.
      • Liu C.M.
      • et al.
      Genetic loci associated with an earlier age at onset in multiplex schizophrenia.
      ), but evidence is still lacking in allergic diseases.
      • Wan J.
      • Mitra N.
      • Hoffstad O.J.
      • Margolis D.J.
      Influence of FLG mutations and TSLP polymorphisms on atopic dermatitis onset age.
      found that FLG mutations are associated with earlier atopic dermatitis (AD) onset.
      • Ferreira M.A.R.
      • Vonk J.M.
      • Baurecht H.
      • Marenholz I.
      • Tian C.
      • Hoffman J.D.
      • et al.
      Age-of-onset information helps identify 76 genetic variants associated with allergic disease.
      performed a GWAS for allergic diseases, including AD, supporting the notion of strong genetic effects on early- and late-onset AD. These are the only studies that have investigated the genetic associations in age of onset for AD and were limited to predominantly European populations. Thus, unraveling the component of age of onset at a genome-wide level for patients with AD in Asian populations would add important insights. Recently, we, to our knowledge, reported previously unreported loci, including Japanese-specific loci, through one of the largest GWAS for AD (
      • Tanaka N.
      • Koido M.
      • Suzuki A.
      • Otomo N.
      • Suetsugu H.
      • Kochi Y.
      • et al.
      Eight novel susceptibility loci and putative causal variants in atopic dermatitis.
      ). Taking advantage of the GWAS results, we investigated further the genetic architectures of AD, underlying the age of onset of AD.

      Abbreviation:

      AD (atopic dermatitis)
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