Dissecting the genetic heterogeneity of myopia susceptibility in an Ashkenazi Jewish population using ordered subset analysis.

Purpose: Despite many years of research, most of the genetic factors contributing to myopia development remain unknown. Genetic studies have pointed to a strong inherited component, but although many candidate regions have been implicated, few genes have been positively identified.

Methods: We have previously reported 2 genomewide linkage scans in a population of 63 highly aggregated Ashkenazi Jewish families that identified a locus on chromosome 22.

Genomewide linkage scans for ocular refraction and meta-analysis of four populations in the Myopia Family Study.

Purpose: Genomewide linkage scans were performed in Caucasian (CAUC) and Old Order Amish (OOA) families to identify genomic regions containing genes responsible for refractive error control. We also performed a meta-analysis by combining these results with our previous linkage results from Ashkenazi Jewish (ASHK) and African American (AFRAM) families.

Methods: Two hundred seventy-one CAUC and 411 OOA participants (36 and 61 families, respectively) were recruited to participate in the Myopia Family Study.

Genome-wide scan of African-American and white families for linkage to myopia.

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.

Genomewide scan of ocular refraction in African-American families shows significant linkage to chromosome 7p15.

Refractive development is influenced by environmental and genetic factors. Genetic studies have identified several regions of linkage to ocular refraction, but none have been carried out in African-derived populations. We performed quantitative trait locus linkage analyses in African-American (AA) families to identify genomic regions responsible for refraction.

Genome-wide scan of additional Jewish families confirms linkage of a myopia susceptibility locus to chromosome 22q12.

Purpose: A genome-wide scan was previously reported for myopia in Ashkenazi Jews. In order to confirm the previous linkage peaks, a collection of DNA samples from 19 new Ashkenazi Jewish families were tested for linkage in a genome wide scan.

Methods: Families were ascertained from an Orthodox Ashkenazi Jewish community through mailings.

Genomewide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36.

Unlabelled: The development of refractive error is mediated by both environmental and genetic factors. We performed regression-based quantitative trait locus (QTL) linkage analysis on Ashkenazi Jewish families to identify regions in the genome responsible for ocular refraction. We measured refractive error on individuals in 49 multi-generational American families of Ashkenazi Jewish descent.

Genome-wide scan for myopia in the Old Order Amish.

Purpose: To identify myopia susceptibility genes influencing common myopia in 34 Old Order Amish families, a genetically well-defined founder population.

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.

GeneLink: a database to facilitate genetic studies of complex traits.

Background: In contrast to gene-mapping studies of simple Mendelian disorders, genetic analyses of complex traits are far more challenging, and high quality data management systems are often critical to the success of these projects. To minimize the difficulties inherent in complex trait studies, we have developed GeneLink, a Web-accessible, password-protected Sybase database.

Results: GeneLink is a powerful tool for complex trait mapping, enabling genotypic data to be easily merged with pedigree and extensive phenotypic data.

Candidate high myopia loci on chromosomes 18p and 12q do not play a major role in susceptibility to common myopia.

Background: To determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia.

Methods: Cycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families.

Genomewide linkage scan for myopia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 22q12.

Mild/moderate (common) myopia is a very common disorder, with both genetic and environmental influences. The environmental factors are related to near work and can be measured. There are no known genetic loci for common myopia.

Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis.

Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods.