Gene mapping for primary open angle glaucoma

Primary open angle glaucoma (POAG) is a leading cause of visual impairment and blindness worldwide. To date, at least 20 genetic loci for POAG have been reported. Only 3 causative genes are identified from these loci: myocilin (MYOC), optineurin (OPTN) and WD repeat domain 36 (WDR36), which together account for less than 10% of POAG. Only a portion of POAG follows Mendelian inheritance, and a considerable fraction results from a large number of variants in several genes, each contributing small effects. Over the past 10 years, there has been vigorous research on mapping the POAG genes. The main technological approaches are functional cloning, family linkage analysis, genome-wide scan, case-control association study, and microarray analysis. Association studies found 16 genes related to POAG, but reports on glaucoma-causing effects of these genes are conflicting. Ten microarray gene expression studies related to POAG have been published. A number of genes potentially related to POAG have been identified, and they provide a good resource to select candidate genes for mutation analysis in association studies. While linkage studies remain a mainstay, the current trend is to use genome-wide association studies to map genes for POAG. This review gives an overview of the efforts in the past decade to identify the POAG genes through linkage studies, genome-wide scans, case-control association studies and microarray studies. In the near future such comprehensive studies are expected to greatly advance our understanding of the genetic basis of POAG and provide information for effective glaucoma therapy.