Qtl Mapping for Eye Biometrical Traits

Abstract

Purpose: : Our aim is to identify quantitative trait loci (QTLs) influencing ocular biometrical components using genome-wide approaches in rural homogeneous population isolates. Ocular refraction is a complex quantitative trait with strong but yet poorly elucidated genetic basis. Ocular axial length, cornea and lens are major determinants of refraction, their measurements display close to normal distribution in various population studies and have been shown to display strong heritabilities.

Methods: : A first in depth study has been initiated in the island of Vis, a Croatian island isolate. Blood samples have been collected from 1032 people, together with extensive genealogical and phenotypical data. A complete eye examination including refraction and underlying ocular biometry measurements, axial length (AL), anterior chamber depth (ACD), corneal curvature (CC), corneal thickness (CT) and lens thickness (LT) was performed on 635 subjects using NIDEK refracto_keratometer and an A-scan ultrasound device. Whole genome associations with these traits were performed following a 317,503 SNPs scan (Illumina HumanHap300 array) in 583 individuals, using the analysis package plink and taking relatedness between individuals into account.

Results: : Narrow sense heritabilities were measured using variance component models (using related individuals) adjusting for covariates that included number of school years. These genetic contributions were generally high: 44% for ACD, 81% for CC, 66% CT, 55%(female) non significant (male) for LT and 33%(female) 55%(male) for AL.For all traits, candidates displaying suggestive (P<E-5) association were found. The strongest hit (P=1.12E-7) was found for LT.We are currently seeking replication for the strongest hits in a different study of subjects selected on extreme values of the refractive spectrum in the Western isles of Scotland.

Keywords: gene mapping • refraction