title: Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness.
abstract: Central corneal thickness (CCT) has become an endophenotype of major interest for the genetically complex disorder glaucoma. CCT has a high heritability, and thin CCT is an independent risk factor for the diagnosis and progression of open-angle glaucoma. Genome-wide association studies thus provide genetic loci associated with CCT and potentially related to open-angle glaucoma. The distribution of CCT and prevalence of glaucoma in population-based studies have demonstrated ethnic differences suggesting ethnic-dependent variations in the genetic determinants of CCT. We conducted a genome-wide association study in Caucasians (n = 3,931) from the Gutenberg Health Study (Germany) followed by replication of 30 genome-wide significant SNPs or SNPs of interest (P < 10(-5)) in the Rotterdam Study (The Netherlands, n = 1,418). In a combined analysis, we confirmed quantitative trait loci on chromosomes 9q34 and 16q24 for association with CCT. On chromosome 16q24, the locus is located in an intergenic region near the ZNF469 gene (top SNP: rs9938149, P = 1.45 × 10(-12)). ZNF469 missense mutation is involved in a syndrome with very thin cornea (brittle cornea syndrome). The second locus on chromosome 9q34 represents the intergenic region between the RXRA and COL5A1 gene (top SNP: rs3132306, P = 2.71 × 10(-10)). Collagen type 5 determines the diameter of the corneal collagen fibrils. In our Caucasian population-based GWA study, we reinforce the involvement of collagen-related genes influencing CCT in Caucasians. We could not confirm the collagen type 8 locus on chromosome 1 as reported in Asian studies.
authors: Department of Ophthalmology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. rene.hoehn@unimedizin-mainz.de
authors: René
authors: R
authors: Hoehn
authors: Tanja
authors: T
authors: Zeller
authors: Virginie J M
authors: VJ
authors: Verhoeven
authors: Franz
authors: F
authors: Grus
authors: Max
authors: M
authors: Adler
authors: Roger C
authors: RC
authors: Wolfs
authors: André G
authors: AG
authors: Uitterlinden
authors: Raphaële
authors: R
authors: Castagne
authors: Arne
authors: A
authors: Schillert
authors: Caroline C W
authors: CC
authors: Klaver
authors: Norbert
authors: N
authors: Pfeiffer
authors: Alireza
authors: A
authors: Mirshahi
mesh_terms: D000328:Adult; D000368:Aged; D024062:Collagen Type V / Q000235:genetics*; D024102:Collagen Type VIII / Q000235:genetics*; D003315:Cornea / Q000473:pathology*; D055106:Genome-Wide Association Study; D005858:Germany / Q000453:epidemiology; D005901:Glaucoma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D040641:Quantitative Trait Loci; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C530725:COL5A1 protein, human; C443712:COL8A2 protein, human; D024062:Collagen Type V; D024102:Collagen Type VIII; D014157:Transcription Factors; C530065:ZNF469 protein, human