Jensen Richard A, Sim Xueling, Smith Albert Vernon, Li Xiaohui, Jakobsdóttir Jóhanna, Cheng Ching-Yu, Brody Jennifer A, Cotch Mary Frances, Mcknight Barbara, Klein Ronald, Wang Jie Jin, Kifley Annette, Harris Tamara B, Launer Lenore J, Taylor Kent D, Klein Barbara E K, Raffel Leslie J, Li Xiang, Ikram M Arfan, Klaver Caroline C, van der Lee Sven J, Mutlu Unal, Hofman Albert, Uitterlinden André G, Liu Chunyu, Kraja Aldi T, Mitchell Paul, Gudnason Vilmundur, Rotter Jerome I, Boerwinkle Eric, van Duijn Cornelia M, Psaty Bruce M, Wong Tien Y
Circ Cardiovasc Genet. 2016 Feb;9(1):45-54. doi: 10.1161/CIRCGENETICS.115.001142. Epub 2015 Nov 13.
There is increasing evidence that retinal microvascular diameters are associated with cardiovascular 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.
This study extends previous genome-wide association study results using 24 000+ multiethnic participants from 7 discovery cohorts and 5000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single-nucleotide polymorphisms and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent and the central retinal arteriole equivalent. We report 4 new loci associated with central retinal venule equivalent, one of which is also associated with central retinal arteriole equivalent. The 4 single-nucleotide polymorphisms are rs7926971 in TEAD1 (P=3.1×10(-) (11); minor allele frequency=0.43), rs201259422 in TSPAN10 (P=4.4×10(-9); minor allele frequency=0.27), rs5442 in GNB3 (P=7.0×10(-10); minor allele frequency=0.05), and rs1800407 in OCA2 (P=3.4×10(-8); minor allele frequency=0.05). The latter single-nucleotide polymorphism, rs1800407, was also associated with central retinal arteriole equivalent (P=6.5×10(-12)). Results from the gene-based burden tests were null. In phenotype look-ups, single-nucleotide polymorphism rs201255422 was associated with both systolic (P=0.001) and diastolic blood pressures (P=8.3×10(-04)).
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.
越来越多的证据表明，视网膜微血管直径与心血管和脑血管疾病有关。目前尚不清楚这些关联的共同遗传效应。本研究的目的是加深我们对介导视网膜血管大小的遗传因素的理解。
本研究扩展了先前全基因组关联研究的结果，使用了来自7个发现队列的24000多名多民族参与者以及来自2个重复队列的5000多名欧洲血统受试者。使用Illumina HumanExome BeadChip，我们研究了跨基因的单核苷酸多态性和变异与视网膜血管直径汇总测量值（称为视网膜中央静脉当量和视网膜中央动脉当量）之间的关联。我们报告了4个与视网膜中央静脉当量相关的新基因座，其中一个也与视网膜中央动脉当量相关。这4个单核苷酸多态性分别是TEAD1中的rs7926971（P = 3.1×10^(-11)；次要等位基因频率 = 0.43）、TSPAN10中的rs201259422（P = 4.4×10^(-9)；次要等位基因频率 = 0.27）、GNB3中的rs5442（P = 7.0×10^(-10)；次要等位基因频率 = 0.05）以及OCA2中的rs1800407（P = 3.4×10^(-8)；次要等位基因频率 = 0.05）。后一个单核苷酸多态性rs1800407也与视网膜中央动脉当量相关（P = 6.5×10^(-12)）。基于基因的负担测试结果为阴性。在表型查找中，单核苷酸多态性rs201255422与收缩压（P = 0.001）和舒张压（P = 8.3×10^(-04)）均相关。
我们的研究扩展了对影响视网膜微血管大小的遗传因素的理解。这些发现也可能为视网膜与全身微血管疾病之间的关系提供见解。
