Fine mapping linkage analysis identifies a novel susceptibility locus for myopia on chromosome 2q37 adjacent to but not overlapping MYP12.

PURPOSE: Myopia (shortsightedness) is one of the most common ocular conditions worldwide and results in blurred distance vision. It is a complex trait influenced by both genetic and environmental factors. We have previously reported linkage of myopia to a 13.01 cM region of chromosome 2q37 in three large multigenerational Australian families that initially overlapped with the known myopia locus, MYP12. The purpose of this study was to perform fine mapping of this region and identify single nucleotide polymorphisms (SNPs) associated with myopia. METHODS: Fine mapping linkage analysis was performed on three multigenerational families with common myopia to refine the previously mapped critical interval. SNPs in the region were also genotyped to assess for association with myopia using an independent case-control cohort. RESULTS: The disease interval was refined to a 1.83 cM region that is adjacent to rather than overlapping with the MYP12 locus. Subsequent sequencing of all known and hypothetical genes as well as an association study using an independent myopia case-control cohort showed suggestive but not statistically significant association to two intronic SNPs. CONCLUSIONS: We have identified a novel locus for common myopia on chromosome 2q37.

Heritability and shared environment estimates for myopia and associated ocular biometric traits: the Genes in Myopia (GEM) family study.

To examine the familial correlations, heritability (h(2)) and common environmental components (c(2)) of myopia and ocular biometric traits (all treated as continuous outcomes) in families collected through the Genes in Myopia (GEM) family study in Australia. A total of 132 pedigrees (723 participants) were recruited for this study. All individuals completed a risk factor questionnaire and underwent a detailed eye examination including spherical equivalent (SphE) and ocular biometric measurements of axial length (AL), anterior chamber depth (ACD) and corneal curvature (CC). Familial correlations were calculated and h(2) and c(2) were estimated using a variance component model that assumes a multivariate t distribution within each pedigree. Two definitions of common environments (c(2)) were considered: nuclear family (current) shared environment (Model 1) and sib-ship (childhood) shared environment (Model 2). Population ascertainment adjustment was performed using the Blue Mountains eye study dataset. The trends observed for familial correlations suggested that SphE is influenced by both environmental and genetic factors whereas AL, ACD and CC are predominantly genetically determined. This was largely confirmed by variance components modelling. Heritability estimates (adjusted for age, sex and years of education) from the best fitting ACE model (Model 2, childhood shared environment) were 0.50 +/- 0.05 for SphE, 0.73 +/- 0.04 for AL, 0.78 +/- 0.04 for ACD and 0.16 +/- 0.06 for CC. Childhood environmental effects were significant with c(2) estimated to be 0.33 +/- 0.04 for SphE, 0.06 +/- 0.03 for AL, 0.22 +/- 0.04 for ACD and 0.10 +/- 0.05 for CC. Age was associated with SphE, total years of education was associated with AL and sex was associated with all traits studied. We used a novel and conservative approach to account for and estimate common environmental effects by specifying either nuclear family or sib-ship environment when estimating heritability estimates and showed that all traits examined (SphE, AL, ACD and CC) are heritable, thus reflecting a genetic component. These traits therefore all represent candidates for quantitative trait linkage analyses.