Browsing by Author "Gibson, J.R."
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Item Genome-Wide Linkage Scan for Primary Open Angle Glaucoma: Influences of Ancestry and Age at Diagnosis(2011) Crooks, Kristy R.; Allingham, R.R.; Qin, Xuejun; Yutao, Liu.; Gibson, J.R.; Santiago-Turla, C.; Larocque-Abramson, K.R.; Del Bono, E.; Challa, P.; Akafo, S.; Wiggs, J.L.; Schmidt, S.; Hauser, M.A.Primary open-angle glaucoma (POAG) is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry) were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry). Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry). Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci—GLC1D on chromosome 8 and GLC1I on chromosome 15—were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG.Item Genome-Wide linkage scan for primary open angle glaucoma: Influences of ancestry and age at diagnosis(Public Library of Science, 2013) Crooks, K.R.; Allingham, R.R.; Qin, X.; Liu, Y.; Gibson, J.R.; Santiago-Turla, C.; Larocque-Abramson, K.R.; Del Bono, E.; Challa, P.; Herndon, L.W.; Akafo, S.; Wiggs, J.L.; Schmidt, S.; Hauser, M.A.Primary open-angle glaucoma (POAG) is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry) were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry). Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry). Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci-GLC1D on chromosome 8 and GLC1I on chromosome 15-were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG.Item Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry(Investigative Ophthalmology and Visual Science, 2013-08) Liu, Y.; Hauser, M.A.; Akafo, S.K.; Qin, X.; Miura, S.; Gibson, J.R.; Wheeler, J.; Gaasterland, D.E.; Challa, P.; Herndon, L.W.; Ritch, R.; Moroi, S.E.; Pasquale, L.R.; Girkin, C.A.; Budenz, D.L.; Wiggs, J.L.; Richards, J.E.; Ashley-Koch, A.E.; Allingham, R.R.Purpose. Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. Methods. We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP ≤21 mm Hg) and high pressure glaucoma (HPG, IOP >21 mm Hg). Results. In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. Conclusions. POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population. © 2013 The Association for Research in Vision and Ophthalmology, Inc.