Novel Genetic Loci Associated With Retinal Microvascular Diameter

Abstract

Background There is increasing evidence that retinal microvascular diameters are associated with cardio- and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size. Methods and Results This study extends previous genome-wide association study results using 24,000+ multi-ethnic participants from 7 discovery and 5,000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single nucleotide polymorphisms (SNPs) and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent (CRVE) and the central retinal arteriole equivalent (CRAE). We report 4 new loci associated with CRVE, one of which is also associated with CRAE. The 4 SNPs are rs7926971 in TEAD1 (p=3.1×10−11, minor allele frequency (MAF)=0.43), rs201259422 in TSPAN10 (p=4.4×10−9, MAF=0.27), rs5442 in GNB3 (p=7.0×10−10, MAF=0.05) and rs1800407 in OCA2 (p=3.4×10−8, MAF=0.05). The latter SNP, rs1800407, was also associated with CRAE (p=6.5×10−12). Results from the gene-based burden tests were null. In phenotype look-ups, SNP rs201255422 was associated with both systolic (p=0.001) and diastolic blood pressure (p=8.3×10−04). Conclusions Our study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease.

Novel locus influencing retinal venular tortuosity is also associated with risk of coronary artery disease

“…Although we replicated previously reported loci for CRVE , we did not find any novel genome-wide significant loci for this trait[12]’[14]. In addition, we did not replicate any of the previously reported SNPs associated with CRAE [13].…”

“…Understanding the molecular genetic architecture of retinal vascular features provides a molecular pathophysiological basis linking retinal microvascular features with systemic vascular pathology. Recent genome-wide association studies (GWAS) found number of loci for widely investigated retinal traits including central retinal vein equivalent ( CRVE )[12–14], retinal arteriolar equivalent ( CRAE )[12–14], and optic disc morphology[15]. Evidence suggests retinal vascular tortuosity, another potentially important vascular parameter, is also associated with a range of cardiovascular risk factors [16,17].…”

A Review on the Extraction of Quantitative Retinal Microvascular Image Feature

“…Several studies revealed that there was no association with an arteriolar width decreasing and incident stroke and prevalent stroke rather venular widening was associated with incident stroke [ 18 , 129 ]. AVR was also analyzed to determine the relation between AVR and incident stroke and prevalent stroke as the arteriolar and venular widening is responsible for changing the value of AVR.…”

Independent variant analysis of TEAD1 and OCEL1 in 38 Aicardi syndrome patients

“…The nonsense mutation in TEAD1 found in the single subject of Aicardi syndrome similarly is predicted to affect transcription of downstream targets (Schrauwen et al 2015). A recent publication further reported that a SNP in TEAD1 (rs926971) may influence the size of the retinal microvasculature (Jensen et al 2016). Therefore, it is conceivable that variants in TEAD1 may contribute to the ocular and chorioretinal anomalies observed in a rare subset of girls with Aicardi syndrome.…”

“…A recent publication further reported that a SNP in TEAD1 (rs926971) may influence the size of the retinal microvasculature (Jensen et al. ). Therefore, it is conceivable that variants in TEAD1 may contribute to the ocular and chorioretinal anomalies observed in a rare subset of girls with Aicardi syndrome.…”