Genetic Correlation between Corneal Hysteresis and Vertical Cup-disc Ratio in South Indian Consanguineous Pedigrees

Abstract

Purpose : The genetic correlations between traits can contribute to a better understanding of shared biological pathways and/or causality relationships between traits. Previously we measured 45 ocular quantitative traits in 16 consanguineous pedigrees from South India and completed family-based genome-wide association studies and linkage analyses for each trait. The purpose of this study is to conduct a family-based genetic correlation study in this South Indian population.

Methods : 240 individuals of 16 consanguineous pedigrees from South India were measured for 45 ocular quantitative traits. Genotyping was performed using the Illumina HumanOmni2.5-8 platform. 1,223,314 SNPs were used for whole-genome genetic correlation analyses using bivariate genome-based restricted maximum likelihood (GREML) in genome-wide complex trait analysis (GCTA). A gene-based test was performed using the variance-component test in sequence kernel association test (SKAT). The kinship matrix was created using efficient mixed-model association expedited (EMMAX). Age and sex were included as covariates.

Results : A significant genetic correlation was identified between axial length and corneal curvature (r_g = 0.65, s.e.= 0.10, p = 5.3×10^-7, Bonferroni-corrected p = 7.2×10^-5) confirming previous observations in other populations. Nominal genetic correlations were found for several other trait-pairs, including a novel correlation for corneal hysteresis (CH) and vertical cup-disc ratio (VCDR; r_g = -1.00, s.e.= 0.56, p = 0.02). 7,585 SNPs were shared between CH and VCDR with p < 0.05 and different directions of effect. Gene-based test revealed 3 genes (AIF1L, EPB41L3 and SLC26A3) with p < 0.05 shared between the two traits. Previous studies have shown that AIF1L and EPB41L3 are expressed in the retina while SLC26A3 is expressed in the cornea.

Conclusions : We identified a novel genetic correlation between CH and VCDR in the South Indian population. The inverse genetic correlation between these traits is consistent with the previously observed inverse phenotypic correlation, suggesting that genes associated with decreased CH may contribute to increased VCDR. The discovery of genes contributing to both traits can lead to a better understanding of the shared biological pathways between these traits.

This is a 2020 ARVO Annual Meeting abstract.