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

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.

SUBMITTER: Ferreira MA

PROVIDER: S-EPMC5989923 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Ferreira Manuel A MA Vonk Judith M JM Baurecht Hansjörg H Marenholz Ingo I Tian Chao C Hoffman Joshua D JD Helmer Quinta Q Tillander Annika A Ullemar Vilhelmina V van Dongen Jenny J Lu Yi Y Rüschendorf Franz F Esparza-Gordillo Jorge J Medway Chris W CW Mountjoy Edward E Burrows Kimberley K Hummel Oliver O Grosche Sarah S Brumpton Ben M BM Witte John S JS Hottenga Jouke-Jan JJ Willemsen Gonneke G Zheng Jie J Rodríguez Elke E Hotze Melanie M Franke Andre A Revez Joana A JA Beesley Jonathan J Matheson Melanie C MC Dharmage Shyamali C SC Bain Lisa M LM Fritsche Lars G LG Gabrielsen Maiken E ME Balliu Brunilda B Nielsen Jonas B JB Zhou Wei W Hveem Kristian K Langhammer Arnulf A Holmen Oddgeir L OL Løset Mari M Abecasis Gonçalo R GR Willer Cristen J CJ Arnold Andreas A Homuth Georg G Schmidt Carsten O CO Thompson Philip J PJ Martin Nicholas G NG Duffy David L DL Novak Natalija N Schulz Holger H Karrasch Stefan S Gieger Christian C Strauch Konstantin K Melles Ronald B RB Hinds David A DA Hübner Norbert N Weidinger Stephan S Magnusson Patrik K E PKE Jansen Rick R Jorgenson Eric E Lee Young-Ae YA Boomsma Dorret I DI Almqvist Catarina C Karlsson Robert R Koppelman Gerard H GH Paternoster Lavinia L

Nature genetics 20171030 12

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<sup>-8</sup>), including 73 not previously reported, which implicate 132 nearby genes ...[more]

PMID: 29083406

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Project description:The occurrence of allergic multimorbidity (coexistence of asthma, allergic rhinitis and eczema) has not been evaluated longitudinally from early childhood up to adulthood in a population-based study sample. We aimed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospective follow-up data from two decades of a birth cohort study.In 1990, we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population-based MAS birth cohort study. The sample was purposely risk-enriched by increasing the proportion of children at high allergy risk (i.e. at least 2 allergic family members among parents and siblings) from 19% in the source population to 38% in the final sample. The remaining 62% of all MAS children had a low or no allergy risk. Symptoms, medication and doctor's diagnoses of allergic diseases have been assessed using standardized questionnaires including validated ISAAC questions in 19 follow-up assessments up to age 20. Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant: asthma, allergic rhinitis and eczema.Response at age 20 was 72% (n = 942) of all recruited participants. At age 20, 18.5% (95% CI, 15.0-22.5%) of all participants with allergic parents had 2 or 3 concurrent allergies as compared to only 6.3% (95% CI, 4.3-9.0%) of those with non-allergic parents. At this age, allergic multimorbidity was similar in women and men (12.7% (95% CI, 9.7-16.2%) vs. 11.6% (95% CI, 8.9-14.8%)), whereas single allergic diseases were slightly more common in women than men (24.2% (95% CI, 20.2-28.5%) vs. 20.1% (95% CI, 16.6-24.0%)). Asthma occurred more frequently with coexisting allergic rhinitis and/or eczema than as a single entity from pre-puberty to adulthood.Having parents with allergies is not only a strong predictor to develop any allergy, but it strongly increases the risk of developing allergic multimorbidity. In males and females alike, coexisting allergies were increasingly common throughout adolescence up to adulthood. Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity.

Dataset Information

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

Publications

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

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