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Abstract #27351 Published in IGR 12-4
New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8
Vitart V; Bencic G; Hayward C; Skunca Herman J; Huffman J; Campbell S; Bucan K; Navarro P; Gunjaca G; Marin JHuman Molecular Genetics 2010; 19: 4304-4311
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 ((beta) = 0.23 SD, P = 4.4 null 10(-9)) and rs1536482 ((beta) = 0.22 SD, P = 7.1 null 10(-8)) for which the closest candidate genes (although (greater-than or equal to)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 null 10(-4)) but COL5A1 remained a suggestive association in the combined sample ((beta) = 0.16 SD, P = 1.1 null 10(-6)). Following a larger meta-analysis including recently published CCT GWAS summary data, COL5A1 was genome-wide significant ((beta) = 0.13 SD, P = 5.1 null 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 ((beta) = 0.14 SD, P = 3.5 null 10(-9)). The third new locus (rs6496932), on 15q25.3 ((beta) = 0.13, P = 1.4 null 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 the cell surface. These associations offer mechanistic insights into the regulation of CCT and offer new candidate genes for susceptibility to common disorders in which CCT has been implicated, including primary open-angle glaucoma and keratoconus. (copyright) The Author 2010. Published by Oxford University Press. All rights reserved.
V. Vitart. MRC Human Genetics Unit, IGMM, Edinburgh, United Kingdom. v.vitart@hgu.mrc.ac.uk
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
2.2 Cornea (Part of: 2 Anatomical structures in glaucoma)
