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Abhishek Nag, Pirro Hysi, Cristina Venturini, Ekaterina Yonova, Katie Williams, Christopher Hammond; A genome-wide association study of intra-ocular pressure identifies a novel association in the gene FAM125B in the TwinsUK cohort. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4502.
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Glaucoma is a major cause of visual impairment and the second leading cause of blindness in the world. Efforts to dissect the genetic basis of glaucoma have revealed that common genetic variants in several genes determine susceptibility to glaucoma and its endophenotypes. We performed a genome-wide association study in the TwinsUK cohort (all of confirmed Caucasian ancestry) of intra-ocular pressure (IOP), used as the endophenotype for glaucoma.
The study was carried out in a sample of 2774 subjects with mean age of 56.5 years. IOP was measured using Ocular Response Analyser (ORA-Reichert®, Buffalo, NY), a non-contact air-puff tonometer. The mean IOP was 15.6 mmHg (s.d. = 3.26, range = 7-38). Subjects were genotyped using two genotyping platforms from Illumina: 300K Duo for part of the samples and HumanHap610-Quad array for rest of the samples. Whole genome imputation of the genotypes was performed on the basis of HapMap2. Association testing was performed using Merlin that implements a score-test based method to adjust for the family structure in the subjects.
IOP was significantly associated with rs2286886 at 9q33.3 (beta = 0.56, p = 3.6 x 10-8), which was directly genotyped in FAM125B (Homo sapiens family with sequence similarity 125, member B). Two other SNPs at 9q33.3 (rs2286885 and rs10819167) were also significantly associated with IOP (p < 5x10-8). Adjustment for central corneal thickness (CCT) improved the significance of association for rs2286886 (p = 1.01 x 10-9).
This study has identified genome-wide significant associations between SNPs in FAM125B and IOP. FAM125B codes for a component of the membrane complex involving trafficking of ubiquinated proteins, similar to the Caveolin genes which have been associated with POAG. Replication of this locus, and further examination of FAM125B’s possible role in glaucoma, is required.
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