Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

23andMe Research Team, Holger Schulz, Stefan Karrasch, Christian Gieger, Konstantin Strauch, Ronald B. Melles, David A. Hinds, Norbert Hübner, Stephan Weidinger, Patrik K.E. Magnusson, Rick Jansen, Eric Jorgenson, Young Ae Lee, Catarina Almqvist, Robert Karlsson, Gerard H. Koppelman, Lavinia Paternoster

Research output: Contribution to journalArticleAcademicpeer-review

337 Citations (Scopus)

Abstract

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

Original languageEnglish
Pages (from-to)1752-1757
Number of pages6
JournalNature Genetics
Volume49
Issue number12
Early online date30 Oct 2017
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • Journal Article

Cohort Studies

  • Netherlands Twin Register (NTR)

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