title: Genome-wide association study and meta-analysis of intraocular pressure.
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.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: A Bilge
authors.initials: AB
authors.lastname: Ozel
authors.forename: Sayoko E
authors.initials: SE
authors.lastname: Moroi
authors.forename: David M
authors.initials: DM
authors.lastname: Reed
authors.forename: Melisa
authors.initials: M
authors.lastname: Nika
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Schmidt
authors.forename: Sara
authors.initials: S
authors.lastname: Akbari
authors.forename: Kathleen
authors.initials: K
authors.lastname: Scott
authors.forename: Frank
authors.initials: F
authors.lastname: Rozsa
authors.forename: Hemant
authors.initials: H
authors.lastname: Pawar
authors.forename: David C
authors.initials: DC
authors.lastname: Musch
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lichter
authors.forename: Doug
authors.initials: D
authors.lastname: Gaasterland
authors.forename: Kari
authors.initials: K
authors.lastname: Branham
authors.forename: Jesse
authors.initials: J
authors.lastname: Gilbert
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Garnai
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Mohammad
authors.initials: M
authors.lastname: Othman
authors.forename: John
authors.initials: J
authors.lastname: Heckenlively
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Abecasis
authors.forename: David S
authors.initials: DS
authors.lastname: Friedman
authors.forename: Don
authors.initials: D
authors.lastname: Zack
authors.forename: Allison
authors.initials: A
authors.lastname: Ashley-Koch
authors.forename: Megan
authors.initials: M
authors.lastname: Ulmer
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.forename: Yutao
authors.initials: Y
authors.lastname: Liu
authors.forename: Brian L
authors.initials: BL
authors.lastname: Yaspan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Haines
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.forename: Louis
authors.initials: L
authors.lastname: Pasquale
authors.forename: Janey
authors.initials: J
authors.lastname: Wiggs
authors.forename: Julia E
authors.initials: JE
authors.lastname: Richards
authors.forename: Jun Z
authors.initials: JZ
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015220:Calcium Channels; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D016014:Linear Models; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; C575495:TMCO1 protein, human