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

Gong, T., Kuja-Halkola, R., Harder, A. et al. Commun Biol 7, 1077 (2024). https://doi.org/10.1038/s42003-024-06795-1

Abstract

Associations between phenotypes and polygenic risk scores for

GERD with eczema, allergic rhinitis, and asthma in Swedish twins.

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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