A genome-wide association study meta-analysis of epiretinal membrane in two UK populations

Abstract

Purpose : Epiretinal membrane (ERM) is a common retinal pathology strongly linked with age. Whilst several risk factors have been associated with ERM, its genetics is poorly understood. This study aims to identify genetic variants associated with ERM using genome-wide association studies (GWAS) from the TwinsUK cohort and NICOLA Study.

Methods : Spectral domain macular optical coherence tomography (SD-OCT) scans taken from participants of the TwinsUK cohort (Optovue iVue 100, Optovue, Freemont, CA) and NICOLA Study (Heidelberg Engineering, Heidelberg, Germany) were graded for signs of ERM according to the International Vitreomacular Study Group classification. Cases were defined by the presence of ERM in at least one eye. The genetic associations in the two cohorts were tested by a mixed linear regression model with adjustment for age, sex, and relatedness. Summary statistic results from each cohort were used for a fixed-effect inverse variance meta-analysis.

Results : 2197 participants from TwinsUK (250 cases [mean age 69 years], 1947 controls [mean age 52.5 years]) and 2719 participants from NICOLA (206 cases [mean age 66.7 years], 2513 controls [mean age 57.7 years]) were included. Several single nucleotide polymorphisms (SNPs) in the ABCA1 gene reached genome-wide significance in this meta-analysis, the most significant of which p=2.80x10^-9.

Conclusions : Decreased retinal expression levels of ABCA1 have been linked to retinal inflammation in murine models which may be of relevance in ERM. The results of this exploratory study suggest that SNPs in the ABCA1 gene are associated with ERM which may help develop new insights into understanding its etiology. Larger GWASs are needed to confirm these findings.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.