Distinct Genetic Profiles Associated With Subretinal Drusenoid Deposits and Cardiovascular Risk in Age-Related Macular Degeneration.

AMD patients with subretinal drusenoid deposits (SDDs) exhibited distinct minor allele frequencies in several AMD-associated SNPs compared to those without SDDs.

• The retrospective cohort included 459 AMD patients with genotyping and spectral-domain OCT data.
• SDD status was annotated from spectral-domain OCT data.
• Distinct MAFs were observed in SNPs including CFH, ARMS2, COL4A3, and ARHGAP21.
• 52 AMD-associated single-nucleotide polymorphisms (SNPs) were used in the analysis.

Certain genetic variants were more strongly associated with cardiovascular subtypes in AMD patients with SDDs compared to those without SDDs.

• Cardiovascular diagnoses and procedures were extracted from electronic medical records.
• Variants showed stronger associations with cardiovascular subtypes specifically in the SDD-positive group.
• The study compared minor allele frequencies between SDD-positive and SDD-negative groups within CVD subgroups.

Weighted genetic risk scores related to lipid metabolism and complement pathways were higher among SDD-positive patients within selected cardiovascular disease subgroups.

• Weighted genetic risk scores (GRSs) were calculated from 52 AMD-associated SNPs.
• Higher GRSs for lipid metabolism and complement pathways were found in SDD-positive patients.
• This pattern was observed within selected CVD subgroups rather than across the entire cohort.

Principal component analysis revealed modest but significant separation between genetic profiles of AMD patients with and without SDDs.

• PCA was performed to assess clustering by SDD status within CVD subgroups.
• The separation between genetic profiles was described as 'modest but significant.'
• PCA clustering was assessed specifically within cardiovascular disease subgroups.

SDDs are increasingly recognized as a distinct phenotype in AMD and may be linked to cardiovascular disease.

• The study was designed to explore whether AMD patients with SDDs carry a distinct genetic profile related to CVD risk.
• The findings suggest SDDs may represent a 'genetically and systemically unique AMD phenotype.'
• The authors propose that integrating OCT phenotyping and genomic profiling in AMD may uncover systemic disease associations with implications for precision medicine.