Genome-Wide Association Study for Atopic Dermatitis in the Japanese Population
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which there are considerable genetic contributions. Genome-wide association studies (GWASs) provide an unbiased method to identify the genetic factors of human diseases and phenotypes compre
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Genome-Wide Association Study for Atopic Dermatitis in the Japanese Population Mayumi Tamari and Tomomitsu Hirota
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which there are considerable genetic contributions. Genome-wide association studies (GWASs) provide an unbiased method to identify the genetic factors of human diseases and phenotypes comprehensively. Although it is well known that loss-of-function mutations in FLG are the most significant genetic risk factor for AD, recent GWASs, immunochip analyses, and meta-analyses of GWASs have identified a number of loci associated with AD. Candidate genes identified by GWASs of AD are involved in skin barrier functions and innate and adaptive immune responses. Those findings imply a substantial overlap of genetic components with other autoimmune and inflammatory diseases. Genetic variants may influence molecular phenotypes, including RNA expression and stability, transcription factor binding, DNA methylation, histone modifications, and protein levels. Understanding the functional links between susceptibility variants and phenotypic traits is crucial to improve our knowledge of AD. Further interdisciplinary research is necessary for translation of the genetics of AD into clinical practice. Keywords
Atopic dermatitis • Genome-wide association study • Immunochip analysis Meta-analysis • Genetic variants
M. Tamari, M.D., Ph.D. (*) Professor, The Jikei University School of Medicine, Research Center for Medical Science, Core Research Facilities for Basic Science (Molecular Genetics), 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan e-mail: [email protected] T. Hirota Laboratory for Respiratory and Allergic Diseases, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan © Springer Nature Singapore Pte Ltd. 2018 I. Katayama et al. (eds.), Evolution of Atopic Dermatitis in the 21st Century, https://doi.org/10.1007/978-981-10-5541-6_5
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M. Tamari and T. Hirota
Introduction
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which there is a considerable genetic component [1]. Genome-wide association studies (GWASs) provide an unbiased method to identify the genetic factors of human diseases and phenotypes comprehensively [2]. Imputation is a statistical method used to infer untyped genotypes by employing a reference panel of extensively genotyped individuals [3]. Imputation is useful to combine data from GWASs performed using different platforms for meta-analysis, provides a high-resolution overview of association results, and increases the statistical power to identify associated loci. Recent developments in high-throughput genotyping and imputation technologies have made it possible to identify disease susceptibility loci convincingly. Although it is well known that loss-of-function mutations in FLG (encoding filaggrin) are the most significant genetic risk factor for AD [4], recent GWASs, immunoch
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