Structural variation in retinal blood vessels is associated with global vascular health in humans and may provide a readily accessible indicator of several diseases of vascular origin. We report a meta-analysis of genome-wide association studies (GWAS) for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the GoDARTS (n=1736) and ORCADES (n=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 (ACTN4/CAPN12) for retinal venular tortuosity, and one at 13q34 (COL4A2) for retinal arteriolar tortuosity; these two loci were subsequently confirmed in three independent cohorts. In the combined analysis, the lead SNP at each locus was rs1808382 in ACTN4/CAPN12 (P=2.39×10-13) and rs7991229 in COL4A2, (P=4.66×10-12). Notably, the ACTN4/CAPN12 locus associated with retinal venular tortuosity traits is also associated with coronary artery disease and heart rate. Our findings demonstrate the contribution of genetics to retinal vascular traits, and provide new insights into vascular diseases.

Novel Locus Influencing Retinal Venular Tortuosity Is Also Associated With Risk Of Coronary Artery Disease