Heritability of Retinal Vessel Diameters – A Twin Study

Abstract

Abstract: : Purpose: To assess the relative contribution of genetic and environmental effects on retinal vessel diameters in healthy twins. Methods: This was a cross–sectional study of retinal vessel diameters in 56 monozygotic (MZ) and 50 dizygotic (DZ) same–sex pairs of healthy twins. Retinal trunk vessel diameters were analyzed by computerized image analysis of digital grey–scale disc–centred right eye fundus photographs (50°, 1024x1024 pixels). The grader identified the six largest retinal arterioles and venules coursing through a standard area of 0.5 to 1.0 disc diameters from the optic disc margin using semi–automated vessel tracking software and the revised formula (M.D. Knudtson et al. 2003) to determine central retinal artery equivalent diameter (CRAE), central retinal vein equivalent diameter (CRVE) and central arteriovenous diameter ratio (AVR). The proportion of total variation attributable to genetic factors was expressed as heritability h² = 2(r_mz – r_dz). Results: Mean AVR in the study population (n=212) was 0.6827 ± 0.0469 (mean ± SD) (range 0.561 – 0.795). We found no effect of zygocity on mean AVR (MZ: n=112, mean=0.6801 ± 0.04516 (SD), DZ: n=100, mean = 0.6856 ± 0.0488 (SD) (p = 0.397; C.I._95% = –0.018 to 0.00725). The within–pair numerical difference in AVR in MZ twins was 5.48% ± 4.62%; mean ± SD (range= 0.0% – 18.80%) and in DZ twins it was 6.85% ± 4.84%; mean ± SD (range= 0.41% – 28.55%). AVR Pearson correlation (r) was 0.424 in MZ pairs and 0.336 in DZ pairs, yielding an AVR heritability (h²) of 17.6% (C.I._95% = 4.21% – 30.99%). The most prominent association between AVR and systemic characteristics was with diastolic blood pressure (p < 0.001, multiple regression) increasing diastolic blood pressures being associated with decreasing AVR and decreasing retinal artery diameter. Conclusions: Within–pair variation in AVR was significantly lower in MZ than in DZ twins, enabling estimation of a 17% heritability of AVR, which indicates that the major determinants of retinal trunk vessel diameters are environmental. The most prominent non–genetic component identified in this study was diastolic blood pressure. Blood pressure and genetic effects together explain only a minor fraction of the total variation in AVR within the study population of healthy twins. Prospective follow–up of the twin population will address the predictive value of retinal vessel characteristics in relation to systemic morbidity and mortality.

Keywords: retina • imaging/image analysis: clinical • clinical (human) or epidemiologic studies: risk factor assessment