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M. A. Hauser, S. Schmidt, B. Nemesure, C. Leske, F. Hejtmancik, R. R. Allingham; Replication of the Chromosome 2 Locus for POAG in an Independent Dataset of African Origin. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4037.
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Primary Open Angle Glaucoma (POAG) is a major blinding disease that disproportionately affects individuals of West African descent. We have collected 25 African American and 12 Ghanaian multiplex families suitable for genomic linkage analysis to identify regions harboring susceptibility genes for glaucoma in populations of African origin.
The Illumina Bead Station platform (Linkage Panel IV) was used to genotype these 37 POAG families. After excluding markers that did not meet quality control criteria, 5067 SNPs were analyzed with standard linkage methods. Allele frequencies were very similar in the African American and Ghanaian individuals, so results from both groups were combined during analysis. Some of these families were previously found to carry sequence variants in MYOC that do not segregate with disease status. Other families have been linked to the GLC1I locus on chromosome 15. Linkage analysis was conducted both on the entire dataset, and after removing these subgroups.
We have detected linkage to 2q22-24 with a peak non-parametric LOD* score of 1.7, increasing to 2.3 after removing families linked to GLC1I or carrying MYOC variants. This suggestive linkage corresponds to a peak previously identified by the Barbados Family Study Group. The peak gave a three-point lod score of over 3.5 upon fine mapping (markers D2S117 and D2S2189).
Independent replication in multiple independent datasets is extremely powerful in identifying real linkages that harbor susceptibility genes. We have identified suggestive linkage for POAG in our African American / Ghanaian family dataset, which corresponds to that previously reported in the Barbados family dataset. This replicated peak is being followed up in the Barbados dataset, as well as the African American and Ghanaian familial and case/control datasets.
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