Kirin Mirna, Nagy Reka, MacGillivray Thomas J, Polašek Ozren, Hayward Caroline, Rudan Igor, Campbell Harry, Wild Sarah, Wright Alan F, Wilson James F, Vitart Veronique
aCentre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Scotland, UK bFaculty of Medicine, University of Split, Split, Croatia cMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh dCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
J Hypertens. 2017 Aug;35(8):1646-1659. doi: 10.1097/HJH.0000000000001408.
To examine factors influencing retinal vasculature in two environmentally contrasted, cross-sectional studies of adult participants of European descent and to estimate the extent and specificity of genetic contributions to each retinal vasculature feature.
Retinal images from 1088 participants in the Orkney Complex Disease Study and 387 in the CROATIA-Korčula study, taken using the same nonmydriatic camera system and graded by the same person, were evaluated. Using general linear models, we estimated the influence of an extensive range of systemic risk factors, calculated retinal traits heritabilities and genetic correlations.
Systemic covariates explained little (<4%) of the variation in vessel tortuosity, substantially more (>10%, up to 31.7%) of the variation in vessel width and monofractal dimension. Suggestive not well trodden associations of biological interest included that of urate, tissue plasminogen activator and cardiac PR interval with arteriolar narrowing, that of carotid intima-media thickness with less-tortuous arterioles and of cardiac QT interval with more tortuous venules. The genetic underpinning of tortuosity is largely distinct from that of the other retinal vascular features, whereas that of fractal dimension and vessel width greatly overlaps. The previously recognized influence of ocular axial length on vessel widths was high and can be expected to lead to artefactual genetic associations [genetic correlation with central retinal arteriolar equivalent: -0.53 (standard error 0.11)]. The significant genetic correlation between SBP and central retinal arteriolar equivalent, -0.53 (standard error 0.22) (after adjusting for age, sex and axial length of the eye), augurs more favourably for the discovery of genetic variants relevant to vascular physiology.
在两项针对欧洲血统成年参与者的、环境对比鲜明的横断面研究中，考察影响视网膜血管系统的因素，并估计各视网膜血管特征的遗传贡献程度和特异性。
对奥克尼复杂疾病研究中的1088名参与者以及克罗地亚-科尔丘拉研究中的387名参与者的视网膜图像进行评估，这些图像使用相同的非散瞳相机系统拍摄，并由同一人进行分级。我们使用一般线性模型估计了一系列广泛的全身风险因素的影响，计算了视网膜特征的遗传力和遗传相关性。
全身协变量对血管迂曲度变化的解释不足（<4%），对血管宽度和单分形维数变化的解释则多得多（>10%，高达31.7%）。具有生物学意义的、尚未充分研究的潜在关联包括尿酸、组织纤溶酶原激活剂和心脏PR间期与小动脉狭窄的关联，颈动脉内膜中层厚度与迂曲度较小的小动脉的关联，以及心脏QT间期与迂曲度较大的小静脉的关联。迂曲度的遗传基础在很大程度上与其他视网膜血管特征不同，而分形维数和血管宽度的遗传基础则有很大重叠。先前已认识到的眼轴长度对血管宽度的影响很大，预计会导致人为的遗传关联[与视网膜中央动脉等效直径的遗传相关性：-0.53（标准误0.11）]。收缩压与视网膜中央动脉等效直径之间的显著遗传相关性为-0.53（标准误0.22）（在调整年龄、性别和眼轴长度后），这为发现与血管生理相关的遗传变异带来了更有利的前景。
