Causal links found between GERD, asthma, atopic dermatitis
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Genetic variants related to GERD heightened risks for both asthma and atopic dermatitis by 21%, according to study results published in American Journal of Respiratory and Critical Care Medicine.
Further, asthma is a possible risk factor for atopic dermatitis, a causal pathway that has not been identified before, according to researchers.
“Numerous clinical and epidemiological studies have reported association between asthma and GERD, and a large body of evidence suggests that GERD increases the risk of asthma,” Kwangmi Ahn, PhD, MBA, statistical geneticist at the National Institute of Mental Health, and colleagues wrote. “However, as these observational studies are often limited to cross-sectional design and susceptible to confounding and reverse causation, whether the presence of GERD causally increases the risk for asthma remains unclear.”
In a Mendelian randomization (MR) analysis using genetic variants identified from the UK Biobank, Ahn and colleagues sought to determine if GERD is causally associated with asthma and/or atopic dermatitis in European-ancestry populations.
Researchers used data from the two largest genome-wide association studies on asthma (n = 56,167) and GERD (n = 71,522) to understand the magnitude and direction of causality between the diseases and, for atopic dermatitis, they used the most recent population-level genome-wide association study meta-analysis (n = 22,474) to generate genetic instrumental variables used to predict an association to asthma and/or GERD.
Next, researchers used three methods for MR analyses, all of which demonstrated comparable magnitude of causal estimates.
For example, using a random effect inverse variance-weighted method, researchers observed that genetic predisposition for asthma was related to a 46% increased risk for atopic dermatitis (OR = 1.46; 95% CI, 1.34-1.59), and predisposition for atopic dermatitis was related to a 34% increased risk for asthma (OR = 1.34; 95% CI, 1.24-1.45).
Genetically determined atopic dermatitis did not show a causal relationship with GERD, but genetically determined asthma did slightly increase the risk for GERD (OR = 1.06; 95% CI, 1.03-1.09).
Also, researchers found that the genetic variants related to GERD equally raised the risk for asthma (OR = 1.21; 95% CI, 1.09-1.35) and atopic dermatitis (OR = 1.21; 95% CI, 1.07-1.37) by 21%.
“Taken together, this study established a complex genetic interplay among atopic dermatitis, asthma and GERD in European-ancestry populations,” Ahn and colleagues wrote. “Importantly, our findings not only substantiated the association between asthma and GERD but also uncovered previously unrecognized associations that have clinical implications: 1) asthma is a causal risk factor for atopic dermatitis, and 2) the predisposition to atopic dermatitis, including increased risk of asthma, can arise from specific pathogenic mechanisms manifested by GERD. Further studies are needed for the identification and characterization of the gut-lung-skin axis.”
In an accompanying editorial by Meghan D. Althoff, MD, PhD, and Sunita Sharma, MD, MPH, of the division of pulmonary sciences and critical care medicine at the University of Colorado Anschutz Medical Campus, they wrote that more information on the functional genetic effects that lead to the associations found between asthma, atopic dermatitis and GERD are necessary.
“The largest effect sizes were between atopic dermatitis and asthma,” Althoff and Sharma wrote. “On the one hand, this is not surprising given studies showing shared genetic risk between these diseases. The atopic march theory, however, supposes that some atopic dermatitis serves as a precursor to asthma, and mechanistic studies are needed to determine whether this is the case or whether this relationship reflects simply shared genetic risk.”
Further research on the risks found between asthma and GERD, specifically the genetic variants involved, is also required, Althoff and Sharma added.
“Assuming this relationship is truly bidirectional, as this MR study and epidemiologic data would suggest, there are likely distinct genetic variants associated with each pathway that may help better understand the mechanisms and genetic factors driving the development of each comorbid condition,” they wrote.