Genomewide Scan Among Ashkenazi Families Shows Suggestive Evidence for Linkage of Refractive Error to a Quantitative Trait Locus on Chromosome 1p36

Abstract

Abstract: : Purpose: Refractive error development is thought to be mediated by both environmental and genetic factors. We performed quantitative trait locus (QTL) linkage analysis on Ashkenazi Jewish families to identify regions in the genome responsible for ocular refraction. Methods: We obtained refractive error measurements on individuals in 49 multi–generational American families of Ashkenazi Jewish descent. The average family size was 13.7 individuals and was composed of 3 generations. Recruitment criteria specified that every family contain a minimum of 2 myopic members. The mean spherical equivalent refractive error in the sample population was –3.46D (SD=3.29). Microsatellite genotyping with 387 polymorphic markers was performed on 402 individuals by the Center for Inherited Disease Research. After applying a normalizing transformation to the refractive error data, multipoint regression–based linkage analysis was performed using the statistical package Merlin–regress. We estimated genomewide significance levels by generating random genotypes at each marker in 150 replicates of our pedigrees. Results: A maximum LOD score of 4.12 (p=0.0001) was observed at marker D1S552. The corresponding empirical genomewide p–value was 0.08, providing evidence for suggestive linkage to refractive error. This significance level signifies that a maximum LOD score this high or higher would be expected by chance alone once in every 12.5 genome wide scans if no genes exist for refractive error. Conclusions: We found suggestive evidence for linkage of refractive error to a QTL on chromosome 1p36 in an Ashkenazi Jewish population.

Keywords: linkage analysis • refraction • genetics