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Pirro Hysi, Ching-Yu Cheng, Tin Aung, Jamie Craig, Christopher Hammond, Andrew Lotery, Norbert Pfeiffer, Cornelia van Duijn, Ananth Viswanathan, Janey Wiggs; International meta-analysis of genetic factors influencing intraocular pressure: the International Glaucoma Genetics Consortium Study. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1737. doi: https://doi.org/.
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. Intraocular Pressure (IOP) is a major predictor of glaucoma and currently the only modifiable risk factor in the management of Primary Open Angle Glaucoma. Genome-wide association studies (GWAS) have, to date, identified some common genetic variants associated with IOP (TMCO1, GAS7) and with glaucoma (CDKN2AB, TMCO1, CAV1/2), but only explain a fraction of the heritability of these traits. The International Glaucoma Genetics Consortium (IGGC) aims to identify further genes and genetic pathways that influence IOP, by increasing sample sizes through international GWAS meta-analyses.
GWAS of 2.5 million Single Nucleotide Polymorphisms (SNPs) present in the HapMap2 databases were individually carried out in each of the 15 centers which at the time of submission were contributing to the IGGC IOP project. Association was done using a linear regression model with IOP as an outcome and SNPs as a predictor, adjusting for age and sex. Genetic associations observed for each locus at individual centers were then meta-analyzed together.
Meta-analysis of data from 28,712 participating subjects found strong associations with a number of genetic loci, some of which have been previously described in the literature in relation to glaucoma or IOP. The strongest associations were observed for two genetic loci, within the genetic sequences of the CAV1 (p= 4.8x10-09 for rs10258482) and the GAS7 genes (p=5.5x10-11 for rs9913911) respectively. Interestingly only suggestive association with IOP was observed for the TMCO1 locus (p=4.7x10-07 for rs6696454). Novel loci were also associated on chromosomes 9 and 11 at genome-wide significance level.
The IGGC IOP study is an ongoing project that has confirmed existing and discovered new genetic loci that influence intraocular pressure in the general population.
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