The genetics of POAG in black South Africans: a candidate gene association study

Abstract

Multiple loci have been associated with either primary open angle glaucoma (POAG) or heritable ocular quantitative traits associated with this condition. This study examined the association of these loci with POAG, with central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR) and with diabetes mellitus in a group of black South Africans (215 POAG cases and 214 controls). The population was homogeneous and distinct from other African and European populations. Single SNPs in the MYOC, COL8A2, COL1A1 and ZNF469 gene regions showed marginal associations with POAG. No association with POAG was identified with tagging SNPs in TMCO1, CAV1/CAV2, CYP1B1, COL1A2, COL5A1, CDKN2B/CDKN2BAS-1, SIX1/SIX6 or the chromosome 2p16 regions and there were no associations with CCT or VCDR. However, SNP rs12522383 in WDR36 was associated with diabetes mellitus (p = 0.00008). This first POAG genetic association study in black South Africans has therefore identified associations that require additional investigation in this and other populations to determine their significance. This highlights the need for larger studies in this population if we are to achieve the goal of facilitating early POAG detection and ultimately preventing irreversible blindness from this condition.

Figure 1

Structure analysis of 137 SNPs in common in this data (CASE, POAG; Control, Controls) and in other African populations (SAN, San from Southern Africa; HADZA, Hadzabe from Tanzania; YRI, Yoruba from Nigeria; LWK, Luhya from Kenya; SANDAWE, Sandawe from Tanzania) and a European population (CEU, Utah residents with European ancestry).

Figure 2. Summary of association of SNPs with diabetes mellitus by logistic regression.

The measure of association is represented on the y-axis by -log₁₀(p). The association was calculated by logistic regression adjusted for diagnosis (POAG or control), age and gender. The SNPs represented are in COL8A2 (chromosome 1), MYOC (chromosome 1), CYP1B1 (chromosome 2), Chromosome 2p16 region, WDR36 (chromosome 5), COL1A2 (chromosome 7), CAV1/CAV2 (chromosome 7), CDKN2B (chromosome 9), COL5A1 (chromosome 9), ATOH7 (chromosome 10), SIX1/SIX6 (chromosome 14), ZNF469 (chromosome 16) and COL1A1 (chromosome 17). The blue line represents p = 0.05. The red line represents the Bonferroni corrected P = 0.0003 (0.05/159).