Purpose: Myopia is a common disorder with a large public health impact. Although 12 myopia loci have been reported and heterogeneity for high myopia loci have been demonstrated, replication of high-myopia loci with a common myopia phenotype has not been successful. This study reports the successful replication of MYP12 in three large, multigenerational families with autosomal dominant (AD) common myopia (spherical equivalent [SphE] </= -0.50 D).
Methods: These families contained 49 participants (35 affected). The average spherical equivalent was -2.76 D (range, -0.50 to -10.25 D), average axial length was 24.52 mm (range, 23.05-27.11 mm), and average keratometry was 43.21 D (range, 39.12-47.31 D). Only five individuals in the three families presented with myopia of SphE </= -6.00 D. Glaucoma, keratoconus, lenticonus, and dislocated lens were not present in any study participants. A genomewide scan was performed using a mapping set with 400 markers at approximately 10 cM coverage. Merlin software was used for multipoint linkage analysis based on an AD model with a penetrance of 0.9 and disease allele frequency of 0.013.
Results: Significant linkage with a multipoint parametric LOD score of 3.428 (P = 0.000035) and a multipoint nonparametric (Kong and Cox) LOD score of 2.37 (empiric P < 0.001) was obtained on 2q37.1, with a 1-LOD support interval that overlapped the previously reported MYP12 locus for high myopia.
Conclusions: This study provided evidence that some high-myopia loci may contribute to all degrees of myopia and indicated the likely location of a myopia gene for the low/moderate as well as the high form of myopia.