Development and Validation of Polygenic Scores for Retinal Vessel Calibers

Area of Science:

• Ophthalmology
• Genetics
• Public Health

Background:

• Retinal vessel calibers are heritable, measurable biomarkers of microvascular health.
• Genome-wide association studies (GWASs) have identified genetic heritability for retinal vessel traits.
• Polygenic scores (PGSs) for retinal vessel calibers have not been previously developed.

Purpose of the Study:

• To calculate PGSs for retinal vessel calibers.
• To associate these PGSs with measured retinal vessel phenotypes in older adults.

Main Methods:

• Included 3717 European ancestry individuals (≥70 years) with retinal imaging and genotype data.
• Measured retinal vessel calibers as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE).
• Constructed PGSs using the SBayesRC method and analyzed associations via linear regression.

Main Results:

• Both CRAE and CRVE PGSs were significantly associated with their respective measured retinal vessel calibers (P < 0.0001).
• Each standard deviation increase in PGSs correlated with increased vessel diameter (1.53 µm for CRAE, 3.89 µm for CRVE).
• PGSs explained 6.0% of CRAE and 7.1% of CRVE variance, with a dose-response across quartiles.

Conclusions:

• PGSs for CRAE and CRVE are associated with measured retinal microvascular phenotypes.
• Findings highlight the genetic contribution to retinal vessel caliber.
• Provides insights into mechanisms underlying microvascular and macrovascular health.