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].