Few GWAS significant signals have been detected for POAG, even in studies with very large sample size [9]. It seems that the remaining POAG heritability may be accounted for, by rare variants across multiple genes that all contribute to genetic risk and these are not amenable to discovery using genome-wide association methodology. GWAS are aimed at identifying common SNPs with allele frequency of >5% based on the common variant-common disease hypothesis of disease pathogenesis. These genetic polymorphisms may individually only modestly increase the risk of disease. However, there is increasing evidence that accumulation of rare variants may have a larger impact on complex disease than first thought, and may be responsible for the as yet unaccounted for genetic contribution to some common complex diseases. Recent identification of a rare penetrant variant in AMD as an example [24]. Such variation will be detectable by new methods in next generation sequencing which allows genetic variation to be cataloged for all genic regions or the whole human genome. The genetic variants accounting for the remaining heritability of POAG may be more suited to
