New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8
Abstract
Central corneal thickness (CCT) is a highly heritable trait, which has been proposed to influence disorders of the anterior segment of the eye. A genome-wide association study (GWAS) of CCT was performed in 2269 individuals from three Croatian and one Scottish population. In the discovery set (1445 individuals), two genome-wide significant associations were identified for single nucleotide polymorphisms rs12447690 (β = 0.23 SD, P = 4.4 × 10(-9)) and rs1536482 (β = 0.22 SD, P = 7.1 × 10(-8)) for which the closest candidate genes (although ≥90 kb away) were zinc finger 469 (ZNF469) on 16q24.2 and collagen 5 alpha 1 (COL5A1) on 9q34.2, respectively. Only the ZNF469 association was confirmed in our replication set (824 individuals, P = 8.0 × 10(-4)) but COL5A1 remained a suggestive association in the combined sample (β = 0.16 SD, P = 1.1 × 10(-6)). Following a larger meta-analysis including recently published CCT GWAS summary data, COL5A1 was genome-wide significant (β = 0.13 SD, P = 5.1 × 10(-8)), together with two additional novel loci. The second new locus (defined by rs1034200) was 5 kb from the AVGR8 gene, encoding a putative transcription factor with typical ZNF and KRAB domains, in chromosomal region 13q12.11 (β = 0.14 SD, P = 3.5 × 10(-9)). The third new locus (rs6496932), on 15q25.3 (β = 0.13, P = 1.4 × 10(-8)), was within a wide linkage disequilibrium block extending into the 5' end of the AKAP13 gene, encoding a scaffold protein concerned with signal transduction from…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genome-wide association studies have consistently associated single nucleotide polymorphisms (SNPs) in the vicinity of the ZNF469 locus with central corneal thickness (CCT).
“Genome-wide association studies have consistently associated single nucleotide polymorphisms (SNPs) in the vicinity of the ZNF469 locus with central corneal thickness (CTT) [Lu et al., 2010;Vitart et al., 2010;Vithana et al., 2011;Hoehn et al., 2012;Ulmer et al., 2012]”
From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Vitart et al., 2010
Expression profiling studies suggest that both PRDM5 and ZNF469 might be part of a common pathway regulating the expression of ECM genes such as fibrillary collagens, and several studies have suggested a role for ZNF469 in normal corneal development.
“In addition, expression profiling studies suggest that both PRDM5 and ZNF469 might be part of a common pathway regulating the expression of ECM genes such as fibrillary collagens, and several studies have suggested a role for ZNF469 normal corneal development [Lu et al., 2010;Vitart et al., 2010;Vithana et al., 2011;Rohrbach et al., 2013].”
From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Vitart et al., 2010
Cites
GenABEL: an R library for genome-wide association analysis
Aulchenko, Y. S., Ripke, S., Isaacs, A., & van Duijn, C. M. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm108 · Cited by 1,836 · see citing works
Deleterious Mutations in the Zinc-Finger 469 Gene Cause Brittle Cornea Syndrome
Abu, A., Frydman, M., Marek, D., Pras, E., Nir, U., Reznik-Wolf, H., & Pras, E. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.04.001 · Cited by 139 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Ehlers–Danlos syndromes, rare types
Brady, A. F., Demirdas, S., Fournel‐Gigleux, S., Ghali, N., Giunta, C., Kapferer‐Seebacher, I., Kosho, T., Mendoza‐Londono, R., Pope, M. F., Rohrbach, M., et al. (2017) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31550 · Cited by 249 · see citing works
Burkitt Wright, E. M. M., Spencer, H. L., Daly, S. B., Manson, F. D. C., Zeef, L. A. H., Urquhart, J., Zoppi, N., Bonshek, R., Tosounidis, I., Mohan, M., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.05.007 · Cited by 135 · see citing works
Genetics of the Ehlers–Danlos syndrome: More than collagen disorders
Van Damme, T., Syx, D., Coucke, P., Symoens, S., De Paepe, A., & Malfait, F. (2015) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2015.1022528 · Cited by 4 · see citing works
- Authors
- Vitart, V., Benčić, G., Hayward, C., Škunca Herman, J., Huffman, J., Campbell, S., Bućan, K., Navarro, P., Gunjaca, G., Marin, J., Zgaga, L., Kolčić, I., Polašek, O., Kirin, M., Hastie, N. D., Wilson, J. F., Rudan, I., Campbell, H., Vatavuk, Z., Fleck, B., & Wright, A.
- Affiliations
- Sisters of Charity Hospital (HR)
- Institute of Genetics and Cancer (GB)
- University of Split (HR)
- University of Zagreb (HR)
- University of Edinburgh (GB)
- Princess Alexandra Eye Pavilion (GB)
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-08-18
- Volume
- 19
- Issue
- 21
- Pages
- 4304-4311
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2100298873
- Cited by
- 145
- References
- 2
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 11 · 2020: 16 · 2019: 8 · 2018: 8 · 2017: 14 · 2016: 10 · 2015: 11 · 2014: 12 · 2013: 18 · 2012: 14
- FWCI
- 12.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- central corneal thickness, COL5A1, AKAP13, ZNF469, single nucleotide polymorphisms, genome-wide association study, genetic susceptibility, primary open-angle glaucoma, keratoconus, anterior segment disorders, type V collagen, transcription factors, linkage disequilibrium, meta-analysis, Croatian population, Scottish population
- MeSH terms
- Humans, Proto-Oncogene Proteins, Cohort Studies, Minor Histocompatibility Antigens, Epithelium, Corneal, Polymorphism, Single Nucleotide, Collagen Type V, A Kinase Anchor Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
