TY - JOUR
T1 - Exome array analysis identifies CAV1/CAV2 as a susceptibility locus for intraocular pressure
AU - Chen, Fei
AU - Klein, Alison P.
AU - Klein, Barbara E.K.
AU - Lee, Kristine E.
AU - Truitt, Barbara
AU - Klein, Ronald
AU - Iyengar, Sudha K.
AU - Duggal, Priya
N1 - Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.
PY - 2015
Y1 - 2015
N2 - 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 7.4IOP (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.
AB - 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 7.4IOP (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.
KW - Exome
KW - Intraocular pressure
KW - SNP
UR - http://www.scopus.com/inward/record.url?scp=84921753027&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921753027&partnerID=8YFLogxK
U2 - 10.1167/iovs.14-15204
DO - 10.1167/iovs.14-15204
M3 - Article
C2 - 25525164
AN - SCOPUS:84921753027
SN - 0146-0404
VL - 56
SP - 544
EP - 551
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 1
ER -