Genetic analysis of primary open-angle glaucoma-related risk alleles in a Korean population: the GLAU-GENDISK study.

Abstract

To validate six previously known primary open-angle glaucoma (POAG)-related loci in a Korean population. Representative POAG-related single-nucleotide polymorphisms (SNPs) from six loci (<i>cyclin-dependent kinase 4 inhibitor B antisense RNA 1</i> (<i>CDKN2B)-AS1, sineoculis homeobox homolog 1/sineoculis homeobox homolog 6</i>(<i>SIX1/SIX6</i>)<i>, a</i>tonal BHLH transcription factor 7 (<i>ATOH7</i>)<i>, cell division cycle 7-transforming growth factor beta receptor 3, CAV1, transmembrane and coiled-coil domain family 1</i> (<i>TMCO1</i>) were selected and genotyped from discovery (POAG=309, heathy=5400) and replication cohorts (POAG=310, healthy=5612 and POAG=221, healthy=6244, respectively). Data were analysed using logistic regression to calculate the OR for POAG risk associated with SNP. From the discovery cohort, rs1900004 in <i>ATOH7</i> (OR=1.29, p=0.0024); rs1063192 (OR=0.69, p=0.0006), rs2157719 (OR=0.63, p=0.0007) and rs7865618 (OR=0.63, p=0.0006) in <i>CDKN2B-AS1</i>, and rs10483727 in <i>SIX1/SIX6</i> (OR=0.68, p=7.9E-05) were nominally associated with the risk of POAG. The replication cohorts revealed nominal associations with rs2157719 (OR=0.72, p=0.0135), rs1063192 (OR=0.63, p=0.0007) and rs7865618 (OR=0.52, p=0.0004) in <i>CDKN2B-AS1</i>. A mega-analysis from the entire Korean population revealed significance with rs1063192 (OR=0.77, p=6.0E-05), rs2157719 (OR=0.63, p=0.0007) and rs7865618 (OR=0.58, p=1.9E-06) in <i>CDKN2B-AS1</i> and with rs10483727 in <i>SIX1/SIX6</i> (OR=0.79, p=9.4E-05), with the same direction of effect between the discovery association and the replication sample. Variants near <i>CDKN2B-AS1</i> and <i>SIX1/SIX6</i> may require further investigation to obtain more genetic information on POAG development in a Korean population.