Abstract
Abstract: :
Purpose: As part of the Family Study of Myopia, we calculated the heritability of refractive error in a large multi–generational pedigree using three different methods. Methods: Members of the Irish–Welsh family were recruited through postal questionnaires. Spectacle prescriptions and additional information regarding ocular and systemic conditions were obtained from each subject's optometrist (with the aim of excluding syndromic or secondary causes of refractive error). The spherical refraction of the right eye in the least minus meridian was analysed as the quantitative trait of interest. Heritability was calculated by (1) parent–offspring regression, (2) a polygenic variance components analysis (SOLAR) and (3) a Monte Carlo Markov Chain (Gibbs sampling) method. Results: The pedigree spans 7 generations. Of the 192 subjects in 3 generations still living, 109 have agreed to participate so far and refractive details have been obtained for 96. The heritability of refractive error was significantly greater than zero by all three methods. For models where non–spectacle wearers were classified as unknown or emmetropic, respectively, heritability was estimated as (1) 0.56 and 0.52 (S.E. 0.42 and S.E.= 0.23) by parent–offspring regression, (2) 0.58 and 0.67 (S.E.=0.23 and S.E.=0.20) by SOLAR, and (3) 0.59 and 0.68 (S.E.=0.20 and S.E.=0.17) by MCMC. Using the mode of the posterior densities, the estimated heritabilities from the MCMC analysis (0.62 and 0.73) were marginally higher than those obtained with the ML analysis using SOLAR. Conclusions: Heritability was consistently estimated at between 0.5 – 0.7, with higher values from MCMC analyses, and lower ones from parent–offspring regression. The high heritability for refractive error suggests that the prospects for mapping refractive error susceptibility loci in this family are good. Acknowledgements: This research is funded by grants from the College of Optometrists and the Sir Jules Thorn Charitable Trust. Thanks also to the family involved in the study.
Keywords: genetics • clinical (human) or epidemiologic studies: biostatistics/epidemiology methodology • myopia