Genome-wide Scan of African-American and White Families for Linkage to Myopia

Abstract

PURPOSE To identify myopia susceptibility genes influencing common myopia in 94 African-American and 36 White families. DESIGN A prospective study of families with myopia consisting of a minimum of two individuals affected with myopia. METHODS Extended families consisting of at least two siblings affected with myopia were ascertained. A genome-wide linkage scan using 387 markers was conducted by the Center for Inherited Disease Research. Linkage analyses were conducted with parametric and nonparametric methods. Model-free linkage analysis was performed maximizing over penetrance and over dominance (that is, fitting a wide range of both dominant and recessive models). RESULTS Under the model-free analysis, the maximum two point heterogeneity logarithm of the odds score (MALOD) was 2.87 at D6S1009 in the White cohort and the maximum multipoint MALOD was 2.42 at D12S373-D12S1042 in the same cohort. The nonpara-metric linkage (NPL) maximum multipoint at D6S1035 had a P value of .005. An overall multipoint NPL score was obtained by combining NPL scores from both populations. The highest combined NPL score was observed at D20S478 with a significant P value of .008. Suggestive evidence of linkage in the White cohort mapped to a previously mapped locus on chromosome 11 at D11S1981 (NPL = 2.14; P = .02). CONCLUSIONS Suggestive evidence of linkage to myopia in both African Americans and Whites was seen on chromosome 20 and became more significant when the scores were combined for both groups. The locus on chromosome 11 independently confirms a report by Hammond and associates mapping a myopia quantitative trait locus to this region.

Application of Advanced Statistics in Ophthalmology

“…56 Using averaged ocular measurements therefore has been the convention in linkage study for quantitative trait in the myopia genetics research community. [57][58][59][60] In a few scenarios in which the traits may be moderately or weakly correlated between the two eyes, however, 1 neither the use of data from one eye nor an average from both is appropriate, because of the negligence of phenotypic dissimilarity.…”

IMI – Myopia Genetics Report

“…Although validation of the same markers failed in these candidate genes, other variants appeared associated with common myopia, suggesting genetic overlap between Mendelian and complex myopia 37. Linkage studies using a complex inheritance design found five additional loci 38–42…”

Nature and nurture: the complex genetics of myopia and refractive error

“…Many loci for refraction traits were identified in families who segregated high myopia consistent with autosomal-dominant modes of transmission (119,123,(128)(129)(130)(131)(132). Other loci were mapped using either binary-trait or quantitative-trait linkage analyses of milder refractive errors with complex inheritance (72,73,122,124,133,134). Although differences in phenotype definitions, modes of inheritance, and ascertainment criteria between studies limit the generalizability of linkage results, replication of linkage signals do suggest some etiological overlap.…”