Heritability of Recurrent Aphthous Ulcers: Evidence from a UK Twin Cohort

Genetic factors may contribute to the heritability and susceptibility of recurrent aphthous ulcers (RAU). This study evaluated the heritability of RAU in the TwinsUK registry. Data from 890 twin pairs (319 monozygotic [MZ] and 571 dizygotic [DZ]) were used to estimate the prevalence of RAU in the previous year and 8 subphenotypes. A classical twin design was used to partition the variance in RAU presentation into components attributable to additive genetic (A), common/shared environmental (C), dominance genetic (D), and unique/nonshared environmental (E) effects. A multilevel ACE/ADE model with random effects at both the individual and twin-pair levels was fitted to the prevalence of RAU and each subphenotype separately. RAU prevalence in the previous year was 9.3%, with MZ and DZ twin correlations of 0.59 (95% confidence interval [CI]: 0.37, 0.82) and 0.30 (0.09, 0.82), respectively. The ACE model estimated the heritability of RAU prevalence in the previous year at 55.69% (34.43% to 76.95%). Using stricter RAU criteria yielded similar heritability estimates (58.82% [36.51, 81.14]), reinforcing the robustness of the findings. Among subphenotypes, frequency of episodes (53.61% [33.09, 74.13]) and time between occurrences (53.08% [30.96, 75.19]) showed the largest genetic contribution, while ulcer size had the lowest genetic contribution (40.55% [14.76, 66.33]). Heritability estimates for the number of RAU (50.32%, 95% CI: 25.99, 74.65), healing time (49.24% [27.46, 71.03]), and location in soft tissues (42.85% [12.91, 72.78]) and hard tissues (40.70% [12.43, 68.97]) fell between those values. The findings indicate a genetic contribution to RAU susceptibility, with heritability estimates differing across various phenotypic presentations of the condition.