A Genome-Wide Association Study for Primary Open Angle Glaucoma and Macular Degeneration Reveals Novel Loci

Todd E Scheetz,Thomas L Casavant,Val C Sheffield,Edwin M Stone,John H Fingert,Markus H Kuehn,Kai Wang,James C Folk,Abbot F Clark,Stephen R Russell,H Culver Boldt,Wallace L M Alward,Terry A Braun,Kevin L Knudtson

doi:10.1371/journal.pone.0058657

Abstract

Glaucoma and age-related macular degeneration (AMD) are the two leading causes of visual loss in the United States. We utilized a novel study design to perform a genome-wide association for both primary open angle glaucoma (POAG) and AMD. This study design utilized a two-stage process for hypothesis generation and validation, in which each disease cohort was utilized as a control for the other. A total of 400 POAG patients and 400 AMD patients were ascertained and genotyped at 500,000 loci. This study identified a novel association of complement component 7 (C7) to POAG. Additionally, an association of central corneal thickness, a known risk factor for POAG, was found to be associated with ribophorin II (RPN2). Linked monogenic loci for POAG and AMD were also evaluated for evidence of association, none of which were found to be significantly associated. However, several yielded putative associations requiring validation. Our data suggest that POAG is more genetically complex than AMD, with no common risk alleles of large effect.

Highlights

Age-related macular degeneration (AMD) and glaucoma are leading causes of blindness and visual disability in aging populations
The goal of the current study was to use a novel Genome-wide association studies (GWAS) design to identify additional loci involved in glaucoma and age-related macular degeneration
The first was the HapMap[61] CEU population which is comprised of Centre d’ Etude du Polymorphisme Humain (CEPH) individuals of Caucasian ethnicity

Summary

Introduction

Age-related macular degeneration (AMD) and glaucoma are leading causes of blindness and visual disability in aging populations. These conditions are unrelated, each has a strong genetic component. The glaucomas are a group of diseases that are characterized by injury to the optic nerve and a corresponding pattern of visual loss. These disorders are the second most common cause of irreversible blindness and visual impairment in the United States.[1] The most common form of glaucoma in the United States is primary open angle glaucoma (POAG). Most cases of POAG, and the risk factors of elevated IOP and thin central corneal thickness, are thought to be inherited in a complex fashion[3,4]

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