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“Open-angle glaucoma (OAG) is one of the most common causes of blindness worldwide and the number of affected individuals is expected to increase as the population ages.1 It is characterized by the progressive loss of retinal ganglion cells, resulting in visual field defects beginning in the periphery and progressing centrally. Current guidelines for the Screening, Prognosis, Diagnosis, Management, and Prevention of Glaucoma2 state that individuals at low risk of conversion from glaucoma suspect or ocular hypertension to glaucoma should be monitored, and those at high risk should be considered for treatment. The determination of buy Alectinib who is at risk is based on a range of clinical

risk factors, such as intraocular pressure, migraine, family history, and central corneal thickness.2 The genetic component of glaucoma risk is well recognized. Several high-penetrance genes have been described3 and 4 and genetic testing is available for some BMN 673 cost of these.5 However, most

patients do not carry mutations, and thus the contribution of genetics in risk prediction is currently limited to knowledge of family history, which is notoriously unreliable.6 Several common genetic variants increasing the risk of OAG have recently been identified through genome-wide association studies (GWAS; Table 1). Three studies of white individuals have collectively identified 5 loci.7, 8 and 9 Loci reaching genome-wide significance levels include TMCO1 on chromosome 1q24, 7 CAV1/CAV2 8 on 7q31, a regulatory region on 8q22, 9 the 9p21 locus near CDKN2B-AS1, 7 and 9 and SIX1/SIX6 9 on 14q23. Several of these loci have also been associated with OAG-related quantitative traits, and including intraocular pressure (IOP) and vertical cup-to-disc ratio (VCDR). However, reports from these cross-sectional

studies did not distinguish whether the SNPs are associated with the initiation or progression of OAG. Different genetic factors may be involved with these 2 phases. Two of the loci (9p21 and TMCO1) have been identified in an advanced OAG cohort, suggesting they could be important in disease progression leading to the observed enrichment in advanced disease. Both regions are also associated with less severe OAG cases, indicating they may also be important to the vulnerability to OAG and its initiation. 7 There have been no previous reports seeking to examine genetic risk associated with the onset of OAG. To fill in this gap of knowledge, we have undertaken an analysis in an older Australian cohort from the Blue Mountains Eye Study (BMES), to determine whether genetic analysis could inform on the likelihood of an individual’s being diagnosed with glaucoma in the future. The BMES is a well-known longitudinal population-based study of ophthalmic health and disease that includes baseline and 5-year and 10-year follow-up data.