Family aggregation of high myopia: Estimation of the sibling recurrence risk ratio

PURPOSE. To estimate the sibling recurrence risk (K-S) and the sibling recurrence risk ratio (lambda(S)) for high myopia in a cohort in the United Kingdom. METHOD. The recurrence risks for myopia and high myopia were estimated in the siblings of 296 randomly selected high myopes ascertained from an optometric practice population. A model using an age of onset of spectacle wear for myopia of 9.1 +/- 0.7 years or younger was developed as a surrogate for high myopia. The influence of parental myopia on the sibling recurrence risk for high myopia was also evaluated. RESULTS. K-S was estimated (95% confidence limits) to be 10.0% (5.9, 14.8) and lambda(S) to be 4.9 (2.8, 7.6). High myopes without myopic parents were surprisingly common (similar to40%) and were less likely to have highly myopic siblings (K-S similar to6%) than those with at least one myopic parent (K-S similar to14%). CONCLUSIONS. The sibling recurrence risk ratio reported herein (lambda(S) similar to 4.9) implies that the high penetrance autosomal dominant loci for high myopia identified to date account for only a minority of cases of high myopia in the United Kingdom. Furthermore, high-penetrance autosomal dominant inheritance or even high-penetrance recessive inheritance, per se, cannot account for most cases of high myopia. Instead, it may be necessary to consider high myopia as a complex disease resulting from the influence of either alleles of reduced penetrance (susceptibility genes), environmental factors, or both.