A genome-wide scan for primary open-angle glaucoma (POAG): the Barbados Family Study of Open-Angle Glaucoma

Primary open-angle glaucoma (POAG) is characterized by damage to the optic nerve with associated loss of vision. Six named genetic loci have been identified as contributing to POAG susceptibility by genetic linkage analysis of mostly Caucasian families, and two of the six causative genes have been identified. The Barbados Family Study of Open-Angle Glaucoma (BFSG) was designed to evaluate the genetic component of POAG in a population of African descent. A genome-wide scan was performed on 1327 individuals from 146 families in Barbados, West Indies. Linkage results were based on models and parameter estimates derived from a segregation analysis of these families, and on model-free analyses. Two-point LOD scores >1.0 were identified on chromosomes 1, 2, 9, 10, 11, and 14, with increased multipoint LOD scores being found on chromosomes 2, 10, and 14. Fine mapping was subsequently carried out and indicated that POAG may be linked to intervals on chromosome 2q between D2S2188 and D2S2178 and chromosome 10p between D10S1477 and D10S601. Heterogeneity testing strongly supports linkage for glaucoma to at least one of these regions and suggests possible linkages to both. Although TIGR/myocilin and optineurin mutations have been shown to be causally linked to POAG in other populations, findings from this study do not support either of these as causative genes in an Afro-Caribbean population known to have relatively high rates of POAG.