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R R. Allingham, Yutao Liu, Jason Gibson, Joshua Wheeler, Xuejun Qin, Christopher A. Girkin, Stephen K. Akafo, Allison E. Ashley-Koch, POAG African American Study Group, Michael A. Hauser; POAG Genetic Risk Factors In The African American and West African Populations. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4496.
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© ARVO (1962-2015); The Authors (2016-present)
Multiple loci (CDKN2BAS, TMCO1, CAV1/CAV2, and SIX1/SIX6) have been associated with primary open angle glaucoma (POAG) in Caucasian populations. This study examines association of these loci in populations of African ancestry, populations at particularly high risk for POAG.
Fifty tagging SNPs were selected to cover the reported four genomic regions in the African population (YRI). TaqMan-based allelic discrimination assays were used to genotype DNA samples from two populations: African American (1141 cases and 835 controls) and Ghanaian (490 cases and 600 controls). Genetic associations with POAG were evaluated using logistic regression with an additive model, adjusted for age and gender.
In African American samples, no association was identified with tagging SNPs in either TMCO1 or SIX1/SIX6 regions. SNP rs4236601 in the CAV1/CAV2 region showed marginal association with POAG (p value=0.04). Three SNPs (rs10120688, rs16905597, and rs10965245) in the CDKN2BAS region showed marginal association with POAG (p value = 0.02, 0.03, 0.02 respectively). In Ghanaian samples, only three SNPs (rs3807986, rs3815412, and rs8713) in the CDKN2BAS region showed marginal association with POAG (p value = 0.01, 0.03, 0.04 respectively). However, none of these identified associations remained significant after Bonferroni correction for multiple testing. Our African American dataset is well powered to detect association with TMCO1 (97%), CDKN2BAS (98%), and CAV1/CAV2 (79%), while power to detect SIX1/SIX6 is low (30%). Power in the Ghanaian dataset is slightly lower because of a reduced sample size.
Our data indicates that the POAG genetic susceptibility alleles found in Caucasians play a greatly reduced or negligible role in populations of African ancestry, underscoring the critical need to pursue large-scale genome wide association studies in this understudied, yet disproportionately affected population. The POAG African American Study Group includes Janey Wiggs, Julia Richards, Douglas Gaasterland, Paul Lichter, Leon Herndon, Pratap Challa, Robert Ritch, and Donald Budenz.
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