Skip to main content

Genome-wide association studies in asthma: what they really told us about pathogenesis.

Publication ,  Journal Article
Wjst, M; Sargurupremraj, M; Arnold, M
Published in: Curr Opin Allergy Clin Immunol
February 2013

PURPOSE OF REVIEW: Over the past years, several consortia have provided a data deluge from large-scale, genome-wide association studies (GWASs) for numerous asthma and allergy related traits. Dozens of reviews have already summarized the main results, although a coherent picture is still missing, referred to as 'missing' or 'unexplained' heritability. RECENT FINDINGS: We identify the factors responsible for the unexplained heritability including imprecise phenotyping, biased single-nucleotide polymorphism selection (preferentially gene-based and high allele frequency with poor linkage disequilibrium tagging capacity), heterogeneity and insufficient significance ranking test statistics. In spite of these problems, three major outcomes can already be identified. First, rare variants give the highest risk estimates but are limited to small subgroups indicating a complex origin of asthma that may involve hundreds of variants that are either population, family or individual specific. Second, only a few common variants are shared amongst all asthmatics where the IL33/ST2 pathway turns out to be the most relevant factor. Third, transcription factor binding sites are enriched amongst the top association results pointing towards disturbed regulatory network function in asthma. SUMMARY: The next wave of asthma genetic studies will use full-genome sequencing and overcome most GWAS-associated problems. It will be the last step of a century-long search for asthma genes, satisfying scientific curiosity and, hopefully, also providing data applicable in translational medicine.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Curr Opin Allergy Clin Immunol

DOI

EISSN

1473-6322

Publication Date

February 2013

Volume

13

Issue

1

Start / End Page

112 / 118

Location

United States

Related Subject Headings

  • Translational Research, Biomedical
  • Receptors, Cell Surface
  • Polymorphism, Single Nucleotide
  • Interleukins
  • Interleukin-33
  • Interleukin-1 Receptor-Like 1 Protein
  • Humans
  • Genome-Wide Association Study
  • Basic Helix-Loop-Helix Transcription Factors
  • Asthma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wjst, M., Sargurupremraj, M., & Arnold, M. (2013). Genome-wide association studies in asthma: what they really told us about pathogenesis. Curr Opin Allergy Clin Immunol, 13(1), 112–118. https://doi.org/10.1097/ACI.0b013e32835c1674
Wjst, Matthias, Muralidharan Sargurupremraj, and Matthias Arnold. “Genome-wide association studies in asthma: what they really told us about pathogenesis.Curr Opin Allergy Clin Immunol 13, no. 1 (February 2013): 112–18. https://doi.org/10.1097/ACI.0b013e32835c1674.
Wjst M, Sargurupremraj M, Arnold M. Genome-wide association studies in asthma: what they really told us about pathogenesis. Curr Opin Allergy Clin Immunol. 2013 Feb;13(1):112–8.
Wjst, Matthias, et al. “Genome-wide association studies in asthma: what they really told us about pathogenesis.Curr Opin Allergy Clin Immunol, vol. 13, no. 1, Feb. 2013, pp. 112–18. Pubmed, doi:10.1097/ACI.0b013e32835c1674.
Wjst M, Sargurupremraj M, Arnold M. Genome-wide association studies in asthma: what they really told us about pathogenesis. Curr Opin Allergy Clin Immunol. 2013 Feb;13(1):112–118.

Published In

Curr Opin Allergy Clin Immunol

DOI

EISSN

1473-6322

Publication Date

February 2013

Volume

13

Issue

1

Start / End Page

112 / 118

Location

United States

Related Subject Headings

  • Translational Research, Biomedical
  • Receptors, Cell Surface
  • Polymorphism, Single Nucleotide
  • Interleukins
  • Interleukin-33
  • Interleukin-1 Receptor-Like 1 Protein
  • Humans
  • Genome-Wide Association Study
  • Basic Helix-Loop-Helix Transcription Factors
  • Asthma