Abstract
Purpose :
Since the advent of genomic approaches, many chromosomal regions and polymorphisms have been associated with age-related macular degeneration (AMD). However, most of the disease variability might not be still captured by current researched genetic markers due to power issues. We have evidence that at least one component of the sarcoglycan-sarcospan protein complex (Sg-Sspn) gene is associated with increased odds of geographic atrophy (GA) AMD. Moreover, the retina of the knocked-out mouse model for the Sg-Sspn phenotypically resembles GA. Here, we aimed to explore the genome-wide association of the Sg-Sspn complex gene regions with AMD.
Methods :
We analyzed data from two large AMD GWAs: the AREDS (discovery) and the AMD-MMAP (replication, validation) cohort studies. We obtained genotype and phenotype data from the NCBI through the database of Genotypes and Phenotypes. We aimed to test if any single-nucleotide polymorphisms (SNPs) in the Sg-Sspn components were significantly associated with either any AMD diagnosis, a phenotype (GA vs. neovascular -NV-), both phenotypes concurrently at baseline, and GA to NV progression. All analyses were performed on PLINK v.1.9, Perl v. 5.30.0, and R v.3.6.1.
Results :
There were 258 SNPs, controlled for age, sex, and smoking status, with a significant association above our proposed significance level. Out of those, ordering by p-value and q-value, gamma-sarcoglycan (SGCG) appears to be the most strongly associated SNP with any diagnosis of AMD at baseline, followed by delta-sarcoglycan (SGCD). Among progressors, we identified 227 variants above our significance threshold. Once more, SGCG appears as the most significant SNP associated with a 22% increased odds of progression. So far, we fail to evidence that any SNPs in SGCA and SGCB genes are significantly associated with AMD in genome-wide data from Illumina or Affymetrix genotyping platforms.
Conclusions :
Our preliminary analysis indicates that the Sg-Sspn complex is a potential novel genomic region whose contribution to AMD development, phenotype, and progression is not uncovered so far. Nevertheless, our results warrant future study and replication in other populations.
This is a 2020 ARVO Annual Meeting abstract.