Ocular Biometry: Heritability and Identification of Quantitative Traits Loci in a Sardinian Isolated Population

Abstract

Abstract: : Purpose The aim of the study is to assess the heritability of biometric ocular traits in a Sardinian isolated population and to perform a genome wide scan (GWS) to identify the genetic loci associated with these traits, taking advantage of the special characteristics of this population. Methods This study was conducted in Talana, an isolated village in western Sardinia whose demographic history exhibits ancient origin, low number of founders, high inbreeding and genealogical trees reconstructable from 1640. Volunteers from Talana (N=671, aged 5-89 years, 402 females) have undergone a complete eye examination including ocular biometry: axial length (AL), anterior chamber depth (ACD) and corneal curvature (CC) were measured. 59 people were excluded for high myopia, eye surgery or injury which might have altered corneal integrity. Heritability analysis was performed by means of two methods: parent-offspring regression models on 164 nuclear families (N=602) and variance component models on 3-4 generations pedigrees (N= 477). GWS was performed using 654 microsatellite markers spanning the genome. Two and multipoint linkage analysis were performed by the SOLAR package. Results The biometric traits we analysed were normally distributed with values comparable to other populations; furthermore right eyes demonstrated the same pattern of left eyes. The heritability estimates obtained by means of parent offspring regressions and variance components were consistent and significant. CC (mean value 7.67 ± 0.25) had an heritability estimate of 62%. AL (mean value 23.49 ± 0.91) and ACD (mean value 3.45 ± 0.34) were found to have significantly different variances (P<0.01) in males and females so that heritability had to be calculated separately for each sex in the parent offspring regression models. AL had an estimated heritability in females of 30% and in males of 74%, whereas ACD had an estimated heritability in females of 41% and of 46% in males. Suggestive evidences of linkage in multipoint analysis (LOD>2) were identified on chromosomes 6, 7, 14 and 15 for ACD on chromosomes 6 and 12 for CC and on chromosome 2 for AL. Conclusions High heritability of the ACD, AL and CC were highlighted in our genetically homogeneous population. The observed significant differences in parental transmission deserve further insights. For the first time several loci associated with these QT have been identified proving the potentiality of our approach.

Keywords: genetics • clinical (human) or epidemiologic studies: bio • linkage analysis