PURPOSE OF THE STUDY:
A Mendelian randomization (MR) analysis was applied to determine a causal relationship between gastroesophageal reflux disease (GERD) and atopic disorders, including asthma and atopic dermatitis (AD).
STUDY POPULATION:
Genetic data were obtained from the UK Biobank. This information was derived from several genome-wide association studies including cohorts of predominantly White European ancestry (UK, Finland, Estonia, and Australia).
METHODS:
Genetic instrumental variables for asthma, AD, and GERD were obtained from GWAS. Shared genetic correlations between asthma, AD, and GERD were computed. Single nucleotide polymorphisms of each trait were extracted and compared. Causal associations were assessed via a random-effect inverse variance-weighted (IVW), MR-Egger regression and weighted median regression methods.
RESULTS:
The highest genetic correlation was found between AD and asthma. AD was associated with a 34% increased risk for asthma using the IVW method (odds ratio [OR] 1.34; 95% confidence interval [CI], 1.21–1.44, P = 5.77 × 10–10) with similar effect estimates noted between AD and asthma using the weighted median regression and MR-Egger method. When reversed, asthma was associated with a 46% increased risk of AD (odds ratio [OR], 1.46; 95% CI, 1.34–1.59, penalized IVW (P IVW) = 1.67 × 10−18). Regarding GERD and asthma, there was a small significant increased risk of GERD in asthma variants (OR 1.06; 95% CI, 1.03–1.09; P IVW = 4.94 × 10−4) and a larger effect of GERD on increased risk for asthma (OR, 1.21; 95% CI, 1.09–1.35, P IVW = 5.63 × 10−4). Regarding GERD and AD, the effect size of GERD on increased risk of AD was similar to GERD and asthma; however, there was no causal association between AD and increased risk of GERD.
CONCLUSIONS:
In a population of European ancestry, there were causal relationships noted between asthma and AD, asthma and GERD, and AD and GERD. Further studies are warranted to assess mechanisms for these associations.
REVIEWER COMMENTS:
Not surprisingly, this MR analysis demonstrated a strong causal association between AD and asthma, with the most significant association between presence of asthma and increased risk of AD. GERD did appear to play a role in asthma and AD though to much less extent compared with asthma and AD. Understanding the role of the skin, lung, and gut mucosal barriers, as well as the microbiomes associated with each, may help determine mechanisms for development of these atopic disorders such as that future targeted therapies or prevention strategies can be implemented.
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