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Environmental factors play bigger role than genetics in EoE
Eosinophilic esophagitis, or EoE, has been shown to cluster in families, but new research demonstrated that much of this clustering can be attributed to common familial environmental factors.
“The power of this study is the twin analysis,” Eileen Alexander, PhD, MS, BSN, RN, Woodside Fellow at Cincinnati Children’s Hospital Medical Center (CCHMC), said in a press release. “Both the twin and family analyses support that genetics contribute to EoE risk, but the twin analysis revealed that the contribution of genetics was previously overestimated, masking the stronger contribution of common household environment.”
Aiming to estimate the respective influences of environmental and genetic factors on EoE risk in susceptible families, researchers obtained family history from 914 EoE probands seen at the Cincinnati Center for Eosinophilic Disorders at CCHMC between August 2008 and April 2013, plus 2,192 first-degree “nuclear-family” relatives. They also created an international registry of monozygotic and dizygotic EoE twins and triplets (n=63) in 2008, and estimated frequencies, recurrent risk ratios, heritability and twin concordance, and preliminarily examined environmental exposures.
The overall rate of EoE among first-degree relatives in the nuclear-family cohort was 1.8% (2.3% adjusting for sex), and risk for having another child with EoE was 2.4%. Compared with the general population, EoE risk for first-degree relatives was increased 10- to 64-fold, with higher recurrence RRs in brothers (recurrence RR=64; P=.04), fathers (recurrence RR=42.9; P=.004) and males (recurrence RR=50.7; P<.001) compared with sisters, mothers and females, respectively. Monozygotic co-twins had 57.9% proband-wise concordance compared with 36.4% in dizygotic twins (P=.11). Greater birth weight difference between twins (P=.01), breast-feeding (P=.15) and fall birth season (P=.02) were associated with twin discordance in disease status.
Combined gene and common environment heritability was estimated at 72% (P<.001) in the nuclear-family cohort, “suggesting a strong effect from genetics,” according to the researchers. In the twins cohort, however, genetic heritability was an estimated 14.5% (P<.001), and common family environment was estimated at 81% (P<.001), indicating that “heritability estimates are markedly inflated when common environment is not accounted for.”
Marc E. Rothenberg
“This was a very gratifying study, as we developed a hypothesis, called for an international registry to be formed in order to answer this, found an overwhelming interest and support from this by patients, families and health care providers, and then discovered a dataset that has provided deep insight into the etiology of this enigmatic disease," Marc E. Rothenberg, MD, PhD, director of the division of allergy and immunology and Cincinnati Center for Eosinophilic Disorders, Cincinnati Children's Hospital Medical Center, told Healio.com/Gastroenterology. “We have broken down the strong hereditary component into genetics and environment, defined their relative quantification, and uncovered a dominant role for early life exposures.”
Disclosure: See the study for a full list of relevant financial disclosures.