Genome-wide Association Study and Meta-analysis of Intraocular Pressure

Overview

Journal Hum Genet

Specialty Genetics

Date 2013 Sep 5

PMID 24002674

Citations 52

Authors

A Bilge Ozel

Sayoko E Moroi

David M Reed

Melisa Nika

Caroline M Schmidt

Sara Akbari

Kathleen Scott

Frank Rozsa

Hemant Pawar

David C Musch

Paul R Lichter

Doug Gaasterland

Kari Branham

Jesse Gilbert

Sarah J Garnai

Wei Chen

Mohammad Othman

John Heckenlively

Anand Swaroop

Goncalo Abecasis

David S Friedman

Don Zack

Allison Ashley-Koch

Megan Ulmer

Jae H Kang

Yutao Liu

Brian L Yaspan

Jonathan Haines

R Rand Allingham

Michael A Hauser

Louis Pasquale

Janey Wiggs

Julia E Richards

Jun Z Li

Affiliations

Soon will be listed here.

Abstract

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10(-8)). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.

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