Genome-Wide Analysis of Central Corneal Thickness in Primary Open-Angle Glaucoma Cases in the NEIGHBOR and GLAUGEN Consortia
- 1 July 2012
- journal article
- research article
- Published by Association for Research in Vision and Ophthalmology (ARVO) in Investigative Ophthalmology & Visual Science
- Vol. 53 (8), 4468-4474
- https://doi.org/10.1167/iovs.12-9784
Abstract
Purpose.: To investigate the effects of central corneal thickness (CCT)-associated variants on primary open-angle glaucoma (POAG) risk using single nucleotide polymorphisms (SNP) data from the Glaucoma Genes and Environment (GLAUGEN) and National Eye Institute (NEI) Glaucoma Human Genetics Collaboration (NEIGHBOR) consortia. Methods.: A replication analysis of previously reported CCT SNPs was performed in a CCT dataset (n = 1117) and these SNPs were then tested for association with POAG using a larger POAG dataset (n = 6470). Then a CCT genome-wide association study (GWAS) was performed. Top SNPs from this analysis were selected and tested for association with POAG. cDNA libraries from fetal and adult brain and ocular tissue samples were generated and used for candidate gene expression analysis. Results.: Association with one of 20 previously published CCT SNPs was replicated: rs12447690, near the ZNF469 gene (P = 0.001; β = −5.08 μm/allele). None of these SNPs were significantly associated with POAG. In the CCT GWAS, no SNPs reached genome-wide significance. After testing 50 candidate SNPs for association with POAG, one SNP was identified, rs7481514 within the neurotrimin (NTM) gene, that was significantly associated with POAG in a low-tension subset (P = 0.00099; Odds Ratio [OR] = 1.28). Additionally, SNPs in the CNTNAP4 gene showed suggestive association with POAG (top SNP = rs1428758; P = 0.018; OR = 0.84). NTM and CNTNAP4 were shown to be expressed in ocular tissues. Conclusions.: The results suggest previously reported CCT loci are not significantly associated with POAG susceptibility. By performing a quantitative analysis of CCT and a subsequent analysis of POAG, SNPs in two cell adhesion molecules, NTM and CNTNAP4, were identified and may increase POAG susceptibility in a subset of cases.This publication has 31 references indexed in Scilit:
- The NEIGHBOR Consortium Primary Open-Angle Glaucoma Genome-wide Association StudyJournal of Glaucoma, 2013
- Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndromeEuropean Journal of Human Genetics, 2010
- A Genome-Wide Association Study of Optic Disc ParametersPLoS Genetics, 2010
- Common Genetic Variants near the Brittle Cornea Syndrome Locus ZNF469 Influence the Blinding Disease Risk Factor Central Corneal ThicknessPLoS Genetics, 2010
- The gene, environment association studies consortium (GENEVA): maximizing the knowledge obtained from GWAS by collaboration across studies of multiple conditionsGenetic Epidemiology, 2010
- Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genesHuman Genetics, 2009
- Deleterious Mutations in the Zinc-Finger 469 Gene Cause Brittle Cornea SyndromeAmerican Journal of Human Genetics, 2008
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- Principal components analysis corrects for stratification in genome-wide association studiesNature Genetics, 2006
- Identification and Characterization of CEPU-Se—A Secreted Isoform of the IgLON Family Protein, CEPU-1Molecular and Cellular Neuroscience, 2001