New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8

(b 5 0.23 SD, P 5 4.4 3 10 29 ) and rs1536482 (b 5 0.22 SD, P 5 7.1 3 10 28 ) 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 5 8.0 3 10 24 )b utCOL5A1 remained a suggestive association in the combined sample (b 5 0.16 SD, P 5 1.1 3 10 26 ). Following a larger meta-analysis including recently published CCT GWAS summary data, COL5A1 was genome-wide significant (b 5 0.13 SD, P 5 5.1 3 10 28 ), 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 (b 5 0.14 SD, P 5 3.5 3 10 29 ). The third new locus (rs6496932), on 15q25.3 (b 5 0.13, P 5 1.4 3 10 28 ), 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.