We have conducted family-based linkage analysis to identify regions of the genome that may harbor POAG susceptibility variants. These linkage regions provide distinct and complementary data that can assist in the interpretation of genome-wide association studies. The overall dataset and the African ancestry dataset linked POAG to non-overlapping intervals on chromosome 20. As these regions appear to be distinct from the JOAG-linked locus GLC1K, located between D20S846 and rs6081603 
, there may now be as many as three discrete regions of interest on this chromosome alone. The Caucasian ancestry dataset linked POAG to a novel locus on chromosome 1.
Two of the regions with evidence for linkage, 14q11.2 in the combined and Caucasian ancestry datasets and 20p13 in the African ancestry dataset, are telomeric. It is generally accepted that telomeric regions may give rise to false positive linkage peaks at a higher frequency than other regions of the chromosome. In the absence of confirmation, these regions of interest should be considered with caution and follow-up analysis should be delayed until the findings are replicated.
Using OSA, we found increased evidence for linkage in families with adult early-onset on chromosomes 8 and 15, replicating previous findings. The linkage region on chromosome 8 includes the GLC1D locus, which was first reported in a single family with an apparently Mendelian form of glaucoma 
. It is not surprising that the one-lod unit support interval calculated here is somewhat larger than the reported GLC1D locus, considering the differences between a nonparametric linkage analysis of a complex phenotype in a larger family collection, compared to recombination-based linkage mapping within a single large pedigree. Interestingly, the age-at-onset of glaucoma in that pedigree is reported as “within the third to fourth decade of life” which is consistent with the AAD of the OSA-identified subset of families reported here. Our finding suggests the possibility that one or more variants in the GLC1D region may give rise to both rare Mendelian and more common non-Mendelian forms of early-onset POAG.
We have previously reported microsatellite linkage to proximal 15q in a collection of 15 (11 Caucasian and 4 African American) early onset families 
. Our current dataset comprises 34 early-onset families (19 Caucasian ancestry, 15 African ancestry). With the additional families, we were able to divide the dataset based on ancestry and analyze the two groups separately. We replicated linkage to GLC1I in the Caucasian dataset (19 families, including the 11 families reported earlier). In the current report, the one-lod unit support interval is larger and the peak lod score marginally lower than in the previous report. This likely reflects the nature of the individually more informative microsatellite markers compared to SNPs, rather than different underlying genes in the two OSA subsets. There was no evidence for linkage to POAG in the African ancestry early-onset dataset.
In conclusion, we have reported results of the first SNP-based genome-wide linkage analysis of POAG. We identified regions of interest for further investigation in a dataset of African ancestry, a dataset of Caucasian ancestry, and in the combined dataset. We also replicated two previously-reported early-onset POAG loci, strengthening the case that these regions may harbor one or more genes that are either causative for early-onset glaucoma or that modulate the age at which symptoms are first evident. We expect that the results reported here will prove useful in the context of interpreting and strengthening results from genome-wide association studies and will complement efforts to better understand the complex genetic etiology of glaucoma.