title: Novel Genetic Loci Associated With Retinal Microvascular Diameter.
abstract: 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.
  
  
  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.forename: Richard A
authors.initials: RA
authors.lastname: Jensen
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Albert Vernon
authors.initials: AV
authors.lastname: Smith
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Jóhanna
authors.initials: J
authors.lastname: Jakobsdóttir
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Brody
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: Cotch
authors.forename: Barbara
authors.initials: B
authors.lastname: Mcknight
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Annette
authors.initials: A
authors.lastname: Kifley
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Raffel
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Klaver
authors.forename: Sven J
authors.initials: SJ
authors.lastname: van der Lee
authors.forename: Unal
authors.initials: U
authors.lastname: Mutlu
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.forename: Aldi T
authors.initials: AT
authors.lastname: Kraja
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001160:Arterioles; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012161:Retinal Artery; D012169:Retinal Vein; D000091262:TEA Domain Transcription Factors; D059470:Tetraspanins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014699:Venules
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; C554897:TSPAN10 protein, human; D059470:Tetraspanins; D014157:Transcription Factors
keywords: exome; genetics; meta-analysis; microcirculation; retina