Exome array analysis identifies CAV1/CAV2 as a susceptibility locus for intraocular pressure

Fei Chen, Alison P. Klein, Barbara E.K. Klein, Kristine E. Lee, Barbara Truitt, Ronald Klein, Sudha K. Iyengar, Priya Duggal

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


PURPOSE. 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 ¼ 1.2 3 10_5), in GGA3 at 17q25.1 (rs52809447, P ¼ 6.7 3 10_5), and in PKDREJ at 22q13.31 (rs7291444, P ¼ 7.4 3 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 ¼ 7.4

IOP (P ¼ 3.3 3 10_3). This association was confirmed in a meta-analysis with three published genome-wide association studies (Pcombined ¼ 4.0 3 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.

Original languageEnglish (US)
Pages (from-to)544-551
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number1
StatePublished - 2015


  • Exome
  • Intraocular pressure
  • SNP

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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