Meta-analysis identifies seven susceptibility loci involved in the atopic march

Nat Commun. 2015 Nov 6;6:8804. doi: 10.1038/ncomms9804.

Abstract

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Publication types

  • Meta-Analysis

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adolescent
  • Adult
  • Amino Acid Transport Systems, Neutral / genetics
  • Asthma / genetics*
  • Calcium-Binding Proteins / genetics
  • Carrier Proteins / genetics
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics
  • Dermatitis, Atopic / genetics*
  • Disease Progression
  • Female
  • Filaggrin Proteins
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Ikaros Transcription Factor / genetics
  • Interleukin-4 / genetics
  • Kinesins / genetics
  • Logistic Models
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Repressor Proteins / genetics
  • Transcription Factors / genetics
  • Young Adult

Substances

  • AP5B1 protein, human
  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Transport Systems, Neutral
  • Calcium-Binding Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • EFHC1 protein, human
  • EMSY protein, human
  • FLG protein, human
  • Filaggrin Proteins
  • IKZF3 protein, human
  • IL4 protein, human
  • KIF3A protein, human
  • LRRC32 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • OVOL1 protein, human
  • Repressor Proteins
  • SLC6A15 protein, human
  • TMTC2 protein, human
  • Transcription Factors
  • Ikaros Transcription Factor
  • Interleukin-4
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Kinesins