Genetic associations of OCT-derived measures of macula and fovea curvature in UK Biobank participants

Abstract

Purpose : The aim of this study was to identify genetic variants associated with novel measures of the curvature of the posterior globe derived from macular optical coherence tomography (OCT) scans in a large UK-based cohort.

Methods : A total of 73,032 participants from the UK Biobank study who underwent macular spectral-domain OCT as part of their ophthalmic examination were analysed. A deep learning model was used to segment the scans and polynomial fit was used to calculate the curvature of the macula and fovea. Genome-wide association analyses were performed on individuals of European ancestry using BOLT-LMM with adjustment for age, sex and population structure. Given that foveal curvature is highly dependent on retinal pathology individuals were excluded with diabetes or with ocular diagnoses affecting retinal thickness. Given that macula curvature, synonymous with dome-shaped macula configuration, is associated with myopia further analyses with adjustment for refractive error were performed.

Results : Analyses were performed on 77,324 and 58,348 participants for macula and fovea curvature respectively. Genetic variants associated with macula curvature clustered at 37 unique autosomal genomic regions at genome-wide significance (P<5x10-8) and the most significant locus was LAMA2 (p=3.40x10^-49). This and several other loci were previously associated with refractive error and myopia. After adjustment for refractive error the most significant locus was DGKD (p=6.60x10^-65). A larger number genome-wide significant variants were associated with fovea curvature (n=315) which clustered at 128 unique autosomal genomic regions including LINC00461 (p=5.50x10^-76), ADCY5 (p= 5.90x10^-73) and FLT1 (p= 9.90x10^-27).

Conclusions : This study has identified a large number of genetic loci influencing the curvature of the macula and fovea. The identified genetic determinants could provide additional insights into axial elongation, macula staphyloma (a risk factor for myopic maculopathy), dome-shape macula configuration and foveal development.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.