title: Genome-wide association study of retinopathy in individuals without diabetes.
abstract: BACKGROUND
  Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.
  
  
  METHODS
  A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.
  
  
  RESULTS
  No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3±0.23 (beta ± standard error), p = 6.6×10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%), the quality of the imputation was moderate (r(2) ∼0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.
  
  
  CONCLUSIONS
  This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.
authors: Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America. richaj@uw.edu
authors: Richard A
authors: RA
authors: Jensen
authors: Xueling
authors: X
authors: Sim
authors: Xiaohui
authors: X
authors: Li
authors: Mary Frances
authors: MF
authors: Cotch
authors: M Kamran
authors: MK
authors: Ikram
authors: Elizabeth G
authors: EG
authors: Holliday
authors: Gudny
authors: G
authors: Eiriksdottir
authors: Tamara B
authors: TB
authors: Harris
authors: Fridbert
authors: F
authors: Jonasson
authors: Barbara E K
authors: BE
authors: Klein
authors: Lenore J
authors: LJ
authors: Launer
authors: Albert Vernon
authors: AV
authors: Smith
authors: Eric
authors: E
authors: Boerwinkle
authors: Ning
authors: N
authors: Cheung
authors: Alex W
authors: AW
authors: Hewitt
authors: Gerald
authors: G
authors: Liew
authors: Paul
authors: P
authors: Mitchell
authors: Jie Jin
authors: JJ
authors: Wang
authors: John
authors: J
authors: Attia
authors: Rodney
authors: R
authors: Scott
authors: Nicole L
authors: NL
authors: Glazer
authors: Thomas
authors: T
authors: Lumley
authors: Barbara
authors: B
authors: McKnight
authors: Bruce M
authors: BM
authors: Psaty
authors: Kent
authors: K
authors: Taylor
authors: Albert
authors: A
authors: Hofman
authors: Paulus T V M
authors: PT
authors: de Jong
authors: Fernando
authors: F
authors: Rivadeneira
authors: Andre G
authors: AG
authors: Uitterlinden
authors: Wan-Ting
authors: WT
authors: Tay
authors: Yik Ying
authors: YY
authors: Teo
authors: Mark
authors: M
authors: Seielstad
authors: Jianjun
authors: J
authors: Liu
authors: Ching-Yu
authors: CY
authors: Cheng
authors: Seang-Mei
authors: SM
authors: Saw
authors: Tin
authors: T
authors: Aung
authors: Santhi K
authors: SK
authors: Ganesh
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: Mike A
authors: MA
authors: Nalls
authors: Kerri L
authors: KL
authors: Wiggins
authors: Jane Z
authors: JZ
authors: Kuo
authors: Cornelia M
authors: CM
authors: van Duijn
authors: Vilmundur
authors: V
authors: Gudnason
authors: Ronald
authors: R
authors: Klein
authors: David S
authors: DS
authors: Siscovick
authors: Jerome I
authors: JI
authors: Rotter
authors: E Shong
authors: ES
authors: Tai
authors: Johannes
authors: J
authors: Vingerling
authors: Tien Y
authors: TY
authors: Wong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D006973:Hypertension; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012164:Retinal Diseases / Q000235:genetics*
chemical_list: D012097:Repressor Proteins; C486544:HDAC9 protein, human; D006655:Histone Deacetylases
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