Genetics of Atopic Dermatitis

From DNA Sequence to Clinical Relevance

Mari Løset (Lead / Corresponding author), Sara J. Brown, Marit Saunes, Kristian Hveem

Research output: Contribution to journalReview article

Abstract

Atopic dermatitis (AD) is a complex disease that is thought to be triggered by environmental factors in genetically susceptible individuals. Twin studies have estimated the heritability of AD to be approximately 75%, with the null (loss-of-function) mutations of the gene encoding filaggrin (FLG) (chromosome 1q21.3) as the strongest known genetic risk factor. The discovery of the filaggrin gene was important in the emerging model for AD pathogenesis, combining skin barrier function with adaptive and innate immunity. Assisted by the recent development of large-scale high-throughput genomics, more than 30 genetic loci have been linked to AD across different populations. Identification of these loci, together with functional studies, has already provided new insights into disease biology and identified novel drug targets. Further, these susceptibility loci are laying the groundwork for phenome-wide association studies to test their multiple phenotype relationships and application of Mendelian randomization to investigate causal relationships. Despite many known genes, a majority of the genetic risk for AD is yet unexplored. Therefore, studies investigating refined phenotype groups, low-frequency and rare genetic variation, gene-gene and/or gene-environment interactions, epigenetic mechanisms and data from multi-omics technologies are warranted. In this review, we describe genetic discoveries for AD, including results from candidate gene studies, studies of AD-like genetic diseases, genome-wide association studies and genetic sequencing studies. We explain how some of these genetic discoveries have unraveled new mechanistic insights into the pathogenesis of AD and exemplify how personal genetic data could be used for preventive strategies and a tailored treatment regimen (i.e., precision medicine).

Original languageEnglish
Pages (from-to)355-364
Number of pages10
JournalDermatology
Volume235
Issue number5
Early online date14 Jun 2019
DOIs
Publication statusPublished - Aug 2019

Fingerprint

Atopic Dermatitis
Genes
Phenotype
Gene-Environment Interaction
Precision Medicine
Inborn Genetic Diseases
Twin Studies
Genetic Loci
Genome-Wide Association Study
Genetic Association Studies
Adaptive Immunity
Random Allocation
Genomics
Innate Immunity
Epigenomics
Chromosomes
Technology
Skin
Mutation
Pharmaceutical Preparations

Keywords

  • atopic dermatitis
  • Atopic eczema
  • Genetics
  • Genetic association
  • Genome-wide association studies
  • Phenome-wide association studies
  • Sequencing
  • Mendelian randomization

Cite this

Løset, Mari ; Brown, Sara J. ; Saunes, Marit ; Hveem, Kristian. / Genetics of Atopic Dermatitis : From DNA Sequence to Clinical Relevance. In: Dermatology . 2019 ; Vol. 235, No. 5. pp. 355-364.
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title = "Genetics of Atopic Dermatitis: From DNA Sequence to Clinical Relevance",
abstract = "Atopic dermatitis (AD) is a complex disease that is thought to be triggered by environmental factors in genetically susceptible individuals. Twin studies have estimated the heritability of AD to be approximately 75{\%}, with the null (loss-of-function) mutations of the gene encoding filaggrin (FLG) (chromosome 1q21.3) as the strongest known genetic risk factor. The discovery of the filaggrin gene was important in the emerging model for AD pathogenesis, combining skin barrier function with adaptive and innate immunity. Assisted by the recent development of large-scale high-throughput genomics, more than 30 genetic loci have been linked to AD across different populations. Identification of these loci, together with functional studies, has already provided new insights into disease biology and identified novel drug targets. Further, these susceptibility loci are laying the groundwork for phenome-wide association studies to test their multiple phenotype relationships and application of Mendelian randomization to investigate causal relationships. Despite many known genes, a majority of the genetic risk for AD is yet unexplored. Therefore, studies investigating refined phenotype groups, low-frequency and rare genetic variation, gene-gene and/or gene-environment interactions, epigenetic mechanisms and data from multi-omics technologies are warranted. In this review, we describe genetic discoveries for AD, including results from candidate gene studies, studies of AD-like genetic diseases, genome-wide association studies and genetic sequencing studies. We explain how some of these genetic discoveries have unraveled new mechanistic insights into the pathogenesis of AD and exemplify how personal genetic data could be used for preventive strategies and a tailored treatment regimen (i.e., precision medicine).",
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author = "Mari L{\o}set and Brown, {Sara J.} and Marit Saunes and Kristian Hveem",
note = "M.L. and K.H. work in a research unit funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU; the Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. M.L. was supported by a research grant from the Liaison Committee for education, research and innovation in Central Norway. S.J.B. holds a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z).",
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Genetics of Atopic Dermatitis : From DNA Sequence to Clinical Relevance. / Løset, Mari (Lead / Corresponding author); Brown, Sara J.; Saunes, Marit; Hveem, Kristian.

In: Dermatology , Vol. 235, No. 5, 08.2019, p. 355-364.

Research output: Contribution to journalReview article

TY - JOUR

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T2 - From DNA Sequence to Clinical Relevance

AU - Løset, Mari

AU - Brown, Sara J.

AU - Saunes, Marit

AU - Hveem, Kristian

N1 - M.L. and K.H. work in a research unit funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU; the Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. M.L. was supported by a research grant from the Liaison Committee for education, research and innovation in Central Norway. S.J.B. holds a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z).

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