18 Eye Clinic

• Main Authors: Gudmar Thorleifsson, G Bragi Walters, Alex W Hewitt, Gisli Masson, Agnar Helgason, Andrew Dewan, Asgeir Sigurdsson, Adalbjorg Jonasdottir, Sigurjon A Gudjonsson, Kristinn P Magnusson, Hreinn Stefansson, Dennis S C Lam, Pancy O S Tam, Gudrun J Gudmundsdottir, Laura Southgate, Kathryn P Burdon, Maria Soffia Gottfredsdottir, Micheala A Aldred, Paul Mitchell, David St Clair, David A Collier, Nelson Tang, Orn Sveinsson, Stuart Macgregor, Nicholas G Martin, Angela J Cree, Jane Gibson, Alex Macleod, Aby Jacob, Sarah Ennis, Terri L Young, Juliana C N Chan, Wojciech S S Karwatowski, Christopher J Hammond, Kristjan Thordarson, Mingzhi Zhang, Claes Wadelius, Andrew J Lotery, Richard C Trembath, Chi Pui Pang, Josephine Hoh, Jamie E Craig, Augustine Kong, David A Mackey, Fridbert Jonasson, Unnur Thorsteinsdottir, Kari Stefansson
• Other Authors: The Pennsylvania State University CiteSeerX Archives
• Format: Text
• Language: English
• Subjects: Iceland
• Online Access: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1070.8237

We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in ,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q3 (rs423660[A], odds ratio (OR) = .36, P = 5.0 × 0 −0 ). We then replicated the association in sample sets of 2,75 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = .8, P = 0.005) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.002). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG. Glaucoma is the leading cause of irreversible blindness worldwide, affecting approximately 70 million people 1 . It is a chronic degenerative optic neuropathy with progressive loss of retinal ganglion cells and axons resulting in a corresponding thinning of the neuroretinal rim of the optic nerve and a characteristic visual field defect. It is distinct from other forms of optic neuropathy in that the neuro retinal rim of the optic nerve retains its normal pink color as it becomes progressively thinner, leading to an enlarged opticnerve cup. POAG is the most common form of glaucoma. Excluding rare primary juvenile glaucoma with age of onset between 10 and 35 years, POAG is arbitrarily divided into highpressure glaucoma (defined as ≥22 mmHg) and normalpressure glaucoma. POAG is thought to have a multifactorial etiology, with the main risk factors being age, elevated intraocular (IOP) pressure, family history, race, central corneal thickness (CCT), hypertension, diabetes and myopia. The familiality of POAG has been known for decades, and studies have revealed three to ninefold greater risk of POAG in firstdegree relatives of POAG cases than in the population in general 2 . Common variants near CAV1 and CAV2 are associated with primary openangle glaucoma