title: Exome array analysis identifies CAV1/CAV2 as a susceptibility locus for intraocular pressure.
abstract: OBJECTIVE
  Intraocular pressure (IOP) is an important clinical parameter in the evaluation of ocular health. Elevated IOP is a major risk factor for primary open-angle glaucoma (POAG). The goal of this study was to identify rare and less common variants that influence IOP.
  
  
  METHODS
  We performed an exome array analysis in a subset of 1660 individuals from a population-based cohort, the Beaver Dam Eye Study. Associations with IOP were tested on 45,849 single nucleotide variants and 12,390 autosomal genes across the genome.
  
  
  RESULTS
  Intraocular pressure was suggestively associated with novel variants located in FAR2 at 12p11.22 (rs4931170, P = 1.2 × 10(-5)), in GGA3 at 17q25.1 (rs52809447, P = 6.7 × 10(-5)), and in PKDREJ at 22q13.31 (rs7291444, P = 7.4 × 10(-5)). Gene-based analysis found suggestive associations between IOP and the genes HAP1, MTBP, FREM3, and PHF12. We successfully replicated the associations with GAS7 (P = 7.4 × 10(-3)) for IOP, and also identified a previously reported POAG locus in the CAV1/CAV2 region to be associated with IOP (P = 3.3 × 10(-3)). This association was confirmed in a meta-analysis with three published genome-wide association studies (Pcombined = 4.0 × 10(-11)).
  
  
  CONCLUSIONS
  Our results suggest that novel genetic variants and genes with multiple, less common variants may play a role in the control of IOP. The implication of the caveolin genes, CAV1/CAV2, as a common genetic factor influencing both IOP variations and POAG may provide new insights of the underlying mechanism leading to glaucoma and glaucomatous visual field loss.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.
authors.forename: Alison P
authors.initials: AP
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Barbara
authors.initials: B
authors.lastname: Truitt
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.
authors.forename: Priya
authors.initials: P
authors.lastname: Duggal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D051243:Caveolin 2 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D059472:Exome; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D040081:Protein Array Analysis; D012189:Retrospective Studies
chemical_list: C495540:CAV1 protein, human; C495544:CAV2 protein, human; D051242:Caveolin 1; D051243:Caveolin 2; D004247:DNA
keywords: SNP; exome; intraocular pressure