Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness
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Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness. / Hoehn, René; Zeller, Tanja; Verhoeven, Virginie J M; Grus, Franz; Adler, Max; Wolfs, Roger C; Uitterlinden, André G; Castagne, Raphaële; Schillert, Arne; Klaver, Caroline C W; Pfeiffer, Norbert; Mirshahi, Alireza.
In: HUM GENET, Vol. 131, No. 11, 11.2012, p. 1783-1793.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness
AU - Hoehn, René
AU - Zeller, Tanja
AU - Verhoeven, Virginie J M
AU - Grus, Franz
AU - Adler, Max
AU - Wolfs, Roger C
AU - Uitterlinden, André G
AU - Castagne, Raphaële
AU - Schillert, Arne
AU - Klaver, Caroline C W
AU - Pfeiffer, Norbert
AU - Mirshahi, Alireza
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Collagen Type V/genetics
KW - Collagen Type VIII/genetics
KW - Cornea/pathology
KW - European Continental Ancestry Group/genetics
KW - Genome-Wide Association Study
KW - Germany/epidemiology
KW - Glaucoma/epidemiology
KW - Humans
KW - Meta-Analysis as Topic
KW - Middle Aged
KW - Netherlands/epidemiology
KW - Polymorphism, Single Nucleotide/genetics
KW - Prospective Studies
KW - Quantitative Trait Loci
KW - Risk Factors
KW - Transcription Factors/genetics
U2 - 10.1007/s00439-012-1201-3
DO - 10.1007/s00439-012-1201-3
M3 - SCORING: Journal article
C2 - 22814818
VL - 131
SP - 1783
EP - 1793
JO - HUM GENET
JF - HUM GENET
SN - 0340-6717
IS - 11
ER -