Geographic atrophy (GA) is a clinical outcome with a high medical need for effective therapy, and researchers continue to look into the genetic makeup of lesion growth. A genome-wide association study has led one team to suggest the protein arginine methyltransferase 6 gene (PRMT6) and the lanosterol synthase gene (LSS) as the most likely progression-associated genes. Each minor allele of the genome-wide associated variants increased GA growth rate by a mean of about 15%, or 0.05mm per year.

Researchers combined analysis from four independent studies: the Fundus Autofluorescence Imaging in Age-Related Macular Degeneration study, the Directional Spread in Geographic Atrophy study, the Age-Related Eye Disease Study  and the Geographic Atrophy Treatment Evaluation study. The combined data included 935 patients with a mean age of 74.7 years. Both genome-wide significant loci at PRMT6 and LSS jointly explain 6.05% of the observed variation in GA lesion progression. Within the PRMT6 and LSS loci, a total of 13 local genes could be implicated by the respective association signals. Together, genetic and clinical parameters explained 15.7% of disease variability, which the researchers believe underscores the need to consider these findings in future clinical trials targeting GA growth rates.

The data presented provide a basis for investigating the role of the identified candidate genes and pathways on GA lesion growth, the authors argue in their publication.

Grassmann F, Harsch S, Brandl C, et al. Assessment of novel genome-wide significant gene loci and lesion growth in geographic atrophy secondary to age-related macular degeneration. JAMA Ophthalmol. May 23, 2019. [Epub ahead of print].