Professor Jamie Craig
To provide a summary of progress in recruit-ment, and novel gene identification from The Austra-lian and New Zealand Registry of Advanced Glaucoma (ANZRAG).
1300 cases of advanced glaucoma, and 800 secondary glaucoma cases have been recruited by ANZRAG. A Genome wide association study (GWAS) has been completed for advanced glaucoma using a discovery cohort of 590 cases compared with 3956 controls. Further cohorts of advanced glaucoma, and less advanced cases were used to replicate the stron-gest associations from the discovery phase. Similar studies for pseudoexfoliation syndrome (PEX), and homozygosity mapping for developmental glaucoma have also been completed.
The advanced glaucoma GWAS identified genes on chromosome 1q24 (TMCO1) and 9p21 (CDKN2B-AS1) which reached genome wide signi-ficance (OR 1.68, p = 6.1 x 10?10, and OR 1.50, p = 4.7 x 10?9 respectively), and have clearly replicated. The strength of associations was greater in the advanced OAG cases. Genes in both regions are expressed in retinal ganglion cells. For secondary glau-coma, promis ing results for PEX syndrome are being followed up as modifiers of LOXL1 susceptibility, and a new gene for severe developmental glaucoma has been identified.
The severe disease registry and GWAS methodology has successfully defined genetic regions with strong association to OAG. Genes in these regions are likely to be implicated in retinal ganglion cell apop-tosis susceptibility. Continued expansion of the Eye Foundation supported ANZRAG, and referrals from RANZCO Fellows will increase the power to build on the current successes.