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. 2024 Sep 2;7(1):1077.
doi: 10.1038/s42003-024-06795-1.

Shared genetic architecture between gastro-esophageal reflux disease, asthma, and allergic diseases

Tong Gong  1 , Ralf Kuja-Halkola  1 , Arvid Harder  1 , Cecilia Lundholm  1 , Awad I Smew  1 , Kelli Lehto  2 , Anna Andreasson  3 , Yi Lu  1 , Nicholas J Talley  4 , Joëlle A Pasman  1 , Catarina Almqvist  1   5 , Bronwyn K Brew  6   7
Affiliations

Shared genetic architecture between gastro-esophageal reflux disease, asthma, and allergic diseases

Tong Gong et al. Commun Biol. .

Abstract

The aim is to investigate the evidence for shared genetic architecture between each of asthma, allergic rhinitis and eczema with gastro-esophageal reflux disease (GERD). Structural equation models (SEM) and polygenic risk score (PRS) analyses are applied to three Swedish twin cohorts (n = 46,582) and reveal a modest genetic correlation between GERD and asthma of 0.18 and bidirectional PRS and phenotypic associations ranging between OR 1.09-1.14 and no correlations for eczema and allergic rhinitis. Linkage disequilibrium score regression is applied to summary statistics of recently published GERD and asthma/allergic disease genome wide association studies and reveals a genetic correlation of 0.48 for asthma and GERD, and Genomic SEM supports a single latent factor. A gene-/gene-set analysis using MAGMA reveals six pleiotropic genes (two at 12q13.2) associated with asthma and GERD. This study provides evidence that there is a common genetic architecture unique to asthma and GERD that may explain comorbidity and requires further investigation.

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Conflict of interest statement

The authors have no conflict of interest to declare except for Professor Nicholas Talley (NJT). NJTs involvement is all outside the submitted work: Norgine (2021)(IBS interest group), personal fees from Allakos (gastroduodenal eosinophilic disease) (2021), twoXAR Viscera Labs, (USA 2021) (IBS-diarrhea), IsoThrive (2021) (esophageal microbiome), BluMaiden (microbiome advisory board) (2021), Rose Pharma (IBS) (2021), Intrinsic Medicine (2022) (human milk oligosaccharide), Comvita Mānuka Honey (2021) (digestive health), Astra Zeneca (2022). In addition, Dr. Talley has a patent Nepean Dyspepsia Index (NDI) 1998, a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley, “Diagnostic marker for functional gastrointestinal disorders” Australian Provisional Patent Application 2021901692, ”Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis” US Application No. 63/537,725.

Figures

Fig. 1
Fig. 1. Associations between phenotypes and polygenic risk scores for GERD with eczema, allergic rhinitis, and asthma in Swedish twins.
The associations being presented in odds ratios (OR) are statistically significant when the horizontal line of the confidence interval (error bars) does not cross the vertical gray line at the value 1.
Fig. 2
Fig. 2. Common factor (F1) model for all traits as estimated in Genomic SEM.
F1 is a latent common genetic factor of the genetic components of five GWAS phenotypes, i.e., adult-onset and childhood-onset asthma, allergic rhinitis, eczema, and GERD. The loading of adult-onset asthma was fixed to 1 for model identification purposes. One-headed arrows showed path regression estimates from the independent variable to the dependent variables. Standardized path estimates are given with their standard error in parentheses. The latent u variables with circular arrows reflect the residual variance in the genetic indicators not explained by the common factor.
See this image and copyright information in PMC

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