Heritability of the corneal elevation indices; a population based study

In complex diseases like keratoconus, determining the heritability of risk factors to establish intermediate phenotypes facilitates the identification of genes related to the disease. Several studies confirmed the sensitivity and specificity of elevation data in detecting ectatic disease. However, our knowledge of the genetic and environmental factors affecting these diseases is limited. We evaluated the heritability of the elevation data at the corneal apex and thinnest point in households living in underserved rural areas of Iran. The national data were used to select two underserved districts, i.e., Kojur and Shahyun, randomly. Visual acuity measurement, refraction, biomicroscopy and tomographic imaging (Pentacam HR, Oculus, Inc., Lynnwood, WA) were conducted for all subjects above 5 years who were willing to participate in the study. Subjects with a history of corneal dystrophy, ocular surgery or trauma, and the use of contact lenses in the week prior to examinations were excluded. Moreover, the data of families who had lost their father or mother, childless families were not used for heritability analysis. Heritability estimation was used to calculate the familial aggregation of elevation indices. A linear mixed effects model with a random approach was applied for heritability estimation. The effects of confounding variables, including age, sex, and living place were controlled. The R software was used for statistical analysis. Details of Heritability analysis are given in previous reports. Of 3851 selected subjects, 3314 participated in the study. Finally, after applying the exclusion criteria, 1383 subjects from 382 households were analyzed, of whom 754 (54.52%) were female. The mean age of the participants was 37.23± 19.35 years (6–93 years). Heritability was calculated with controlling the effect of age as the only variable that had a significant correlation with the evaluated indices in a linear regression model (P < 0.001). The heritability of anterior and posterior elevation at corneal apex were 38% (95% CI: 35.2–41.1) and 41% (95% CI: 37.5–45.7), respectively. The heritability of anterior and posterior elevation at the thinnest corneal point were 37% (95% CI: 34.2–40.9) and 37% (95% CI: 31.8–41.6), respectively. The heritability of maximum anterior and posterior elevation in the 5 mm central cornea was 16% (95% CI: 13.9–18.2) and 24% (95% CI: 21.1–26.9), respectively. According to the results, the elevation data of the posterior cornea had higher heritability compared to the elevation data of the anterior surface. The relatively low heritability of elevation indices suggests a more prominent role for environmental factors in causing changes in these parameters in our study population. By contrast, the results of a study by Mahroo et al showed a relatively significant role for genetics in elevation data (55–77%). The reason for this difference may be differences in the study population and analytical method. As mentioned earlier, Mahroo et al conducted their study in twins, and since twins have a more common living environment compared to the general population, a higher heritability in twin studies is expected