BACKGROUND: 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. METHODS AND RESULTS: 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)). 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.
BACKGROUND: 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. METHODS AND RESULTS: 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)). 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.
Authors: Jie J Wang; Bronwen Taylor; Tien Y Wong; Brian Chua; Elena Rochtchina; Ronald Klein; Paul Mitchell Journal: Obesity (Silver Spring) Date: 2006-02 Impact factor: 5.002
Authors: Tien Yin Wong; F M Amirul Islam; Ronald Klein; Barbara E K Klein; Mary Frances Cotch; Cecilia Castro; A Richey Sharrett; Eyal Shahar Journal: Invest Ophthalmol Vis Sci Date: 2006-06 Impact factor: 4.799
Authors: Nina C B B Taarnhøj; Michael Larsen; Birgit Sander; Kirsten O Kyvik; Line Kessel; Jesper L Hougaard; Thorkild I A Sørensen Journal: Invest Ophthalmol Vis Sci Date: 2006-08 Impact factor: 4.799
Authors: Tien Yin Wong; Aruna Kamineni; Ronald Klein; A Richey Sharrett; Barbara E Klein; David S Siscovick; Mary Cushman; Bruce B Duncan Journal: Arch Intern Med Date: 2006-11-27
Authors: Athena W P Foong; Seang-Mei Saw; Jing-Liang Loo; Sunny Shen; Seng-Chee Loon; Mohamad Rosman; Tin Aung; Donald T H Tan; E Shyong Tai; Tien Y Wong Journal: Ophthalmic Epidemiol Date: 2007 Jan-Feb Impact factor: 1.648
Authors: Mirna Kirin; Reka Nagy; Thomas J MacGillivray; Ozren Polašek; Caroline Hayward; Igor Rudan; Harry Campbell; Sarah Wild; Alan F Wright; James F Wilson; Veronique Vitart Journal: J Hypertens Date: 2017-08 Impact factor: 4.844
Authors: Bibiana K Y Wong; Vernon R Sutton; Richard A Lewis; Ignatia B Van den Veyver Journal: Mol Genet Genomic Med Date: 2017-01-25 Impact factor: 2.183
Authors: Denis Plotnikov; Rupal L Shah; Jamille N Rodrigues; Phillippa M Cumberland; Jugnoo S Rahi; Pirro G Hysi; Denize Atan; Cathy Williams; Jeremy A Guggenheim Journal: Hum Genet Date: 2019-05-09 Impact factor: 4.132
Authors: Abirami Veluchamy; Lucia Ballerini; Veronique Vitart; Katharina E Schraut; Mirna Kirin; Harry Campbell; Peter K Joshi; Devanjali Relan; Sarah Harris; Ellie Brown; Suraj S Vaidya; Baljean Dhillon; Kaixin Zhou; Ewan R Pearson; Caroline Hayward; Ozren Polasek; Ian J Deary; Thomas MacGillivray; James F Wilson; Emanuele Trucco; Colin N A Palmer; Alexander S F Doney Journal: Arterioscler Thromb Vasc Biol Date: 2019-10-10 Impact factor: 8.311
Authors: Ryan Swan; Sang Jin Kim; J Peter Campbell; R V Paul Chan; Kemal Sonmez; Kent D Taylor; Xiaohui Li; Yii-Der Ida Chen; Jerome I Rotter; Charles Simmons; Michael F Chiang Journal: Ophthalmol Retina Date: 2018-03-08
Authors: Mary C Whitman; Silvio Alessandro Di Gioia; Wai-Man Chan; Alon Gelber; Brandon M Pratt; Jessica L Bell; Thomas E Collins; James A Knowles; Christopher Armoskus; Michele Pato; Carlos Pato; Sherin Shaaban; Sandra Staffieri; Sarah MacKinnon; Gail D E Maconachie; James E Elder; Elias I Traboulsi; Irene Gottlob; David A Mackey; David G Hunter; Elizabeth C Engle Journal: Invest Ophthalmol Vis Sci Date: 2020-08-03 Impact factor: 4.799