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Roberta Farci, Laura Portas, Federico Murgia, Ginevra Biino, Giulia Caminiti, Gianfranca Cappai, Cristina Malloci, Massimiliano Cosso, Maurizio Fossarello, Mario Pirastu; Epidemiology and Exome Variants analysis of Quantitative Traits related to Glaucoma in three Sardinian isolated populations. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3810.
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© ARVO (1962-2015); The Authors (2016-present)
To identify common and rare gene variants associated with Intraocular pressure (IOP), Anterior Chamber Depth (ACD) and Central Corneal Thickness (CCT) using Exome Single Nucleotide Variants, taking advantage of three isolated populations where, because of their peculiar genetic homogeneity, the effect of variants on the traits may be more highlighted.
We carried out a cross-sectional study in 3 small villages (Talana, Baunei and Urzulei) with a complete eye examination (including Biometry and OCT) of about 3300 subjects. The villages, even though they are in the same mountainous region of an isolated area (Ogliastra) in Sardinia, are genetically distant from each other because of different founders, very low intermarriages, high endogamy and consanguinity. However, the three populations share the same lifestyles and environment. The samples were genotyped on the Illumina Human Exome BeadChip array. After quality controls about 49k SNVs (MAF >0.01) were used for GWAS After filtering for confounding factors we tested 2900 individuals for trait-SNP association assuming an additive genetic model and using a linear mixed model to correct for relatedness as implemented in GenABEL. In addition, heritability and population stratification analyses were performed.
Differences among villages in the distribution of traits were observed as summarized in the Table. Heritability (h2) is very high for all biometric traits and low for IOP. Single variant tests identified 4 new significant (p< 4.5e-6) loci on chromosomes 17p13 (IOP), 1p36 (ACD), 1p36 and 2q36 (CCT). In addition several new, already known and village specific, suggestive (p<1e-5) loci were found.
Many of the identified gene variants may be functionally related to glaucoma as reported in literature, showing the effectiveness of our approach. However, we believe the project could be greatly improved by using population-specific variants.
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