PURPOSE: To ascertain if single nucleotide polymorphisms (SNPs) involved in the determination of central corneal thickness, optic disc area, and vertical cup-to-disc ratio (VCDR) also are associated with open-angle glaucoma (OAG). DESIGN: Retrospective case-control genetic association study. METHODS: A total of 16 SNPs associated with central corneal thickness, optic disc area, and VCDR were genotyped in 876 OAG cases and 883 normal controls. To determine if the SNPs were also correlated with OAG severity, the cohort was stratified into advanced OAG (n = 326) and nonadvanced OAG (n = 550). Both the cases and controls were of European descent and were recruited from within Australia. RESULTS: Two VCDR SNPs were found to be significantly associated with OAG after correction for multiple testing. The 2 SNPs were rs10483727, found adjacent to the SIX1 gene (P = 6.2 × 10(-06); odds ratio, 1.38; 95% confidence interval, 1.20 to 1.59), and rs1063192, found within the CDKN2B gene (P = 2.2 × 10(-05); odds ratio, 0.74; 95% confidence interval, 0.64 to 0.85). The CDKN2B variant rs1063192 also was found to be associated more strongly with advanced OAG. CONCLUSIONS: The findings from this study indicate that variants influencing VCDR are also risk alleles for OAG in our Australian cohort of European descent. The identification of SIX1 and CDKN2B as susceptibility loci will assist in understanding the pathologic mechanisms involved in the development of OAG. Crown
PURPOSE: To ascertain if single nucleotide polymorphisms (SNPs) involved in the determination of central corneal thickness, optic disc area, and vertical cup-to-disc ratio (VCDR) also are associated with open-angle glaucoma (OAG). DESIGN: Retrospective case-control genetic association study. METHODS: A total of 16 SNPs associated with central corneal thickness, optic disc area, and VCDR were genotyped in 876 OAG cases and 883 normal controls. To determine if the SNPs were also correlated with OAG severity, the cohort was stratified into advanced OAG (n = 326) and nonadvanced OAG (n = 550). Both the cases and controls were of European descent and were recruited from within Australia. RESULTS: Two VCDR SNPs were found to be significantly associated with OAG after correction for multiple testing. The 2 SNPs were rs10483727, found adjacent to the SIX1 gene (P = 6.2 × 10(-06); odds ratio, 1.38; 95% confidence interval, 1.20 to 1.59), and rs1063192, found within the CDKN2B gene (P = 2.2 × 10(-05); odds ratio, 0.74; 95% confidence interval, 0.64 to 0.85). The CDKN2B variant rs1063192 also was found to be associated more strongly with advanced OAG. CONCLUSIONS: The findings from this study indicate that variants influencing VCDR are also risk alleles for OAG in our Australian cohort of European descent. The identification of SIX1 and CDKN2B as susceptibility loci will assist in understanding the pathologic mechanisms involved in the development of OAG. Crown
Authors: Mark Christopher; Michael D Abràmoff; Li Tang; Mae O Gordon; Michael A Kass; Donald L Budenz; John H Fingert; Todd E Scheetz Journal: Invest Ophthalmol Vis Sci Date: 2015-07 Impact factor: 4.799
Authors: John H Fingert; Alan L Robin; Todd E Scheetz; Young H Kwon; Jeffrey M Liebmann; Robert Ritch; Wallace L M Alward Journal: Trans Am Ophthalmol Soc Date: 2016-08
Authors: Mona S Awadalla; John H Fingert; Benjamin E Roos; Simon Chen; Richard Holmes; Stuart L Graham; Mark Chehade; Anna Galanopolous; Bronwyn Ridge; Emmanuelle Souzeau; Tiger Zhou; Owen M Siggs; Alex W Hewitt; David A Mackey; Kathryn P Burdon; Jamie E Craig Journal: Am J Ophthalmol Date: 2014-10-02 Impact factor: 5.258
Authors: Abraham Kuot; Alex W Hewitt; Grant R Snibson; Emmanuelle Souzeau; Richard Mills; Jamie E Craig; Kathryn P Burdon; Shiwani Sharma Journal: PLoS One Date: 2017-08-23 Impact factor: 3.240
Authors: Natalie A Afshari; Robert P Igo; Nathan J Morris; Dwight Stambolian; Shiwani Sharma; V Lakshmi Pulagam; Steven Dunn; John F Stamler; Barbara J Truitt; Jacqueline Rimmler; Abraham Kuot; Christopher R Croasdale; Xuejun Qin; Kathryn P Burdon; S Amer Riazuddin; Richard Mills; Sonja Klebe; Mollie A Minear; Jiagang Zhao; Elmer Balajonda; George O Rosenwasser; Keith H Baratz; V Vinod Mootha; Sanjay V Patel; Simon G Gregory; Joan E Bailey-Wilson; Marianne O Price; Francis W Price; Jamie E Craig; John H Fingert; John D Gottsch; Anthony J Aldave; Gordon K Klintworth; Jonathan H Lass; Yi-Ju Li; Sudha K Iyengar Journal: Nat Commun Date: 2017-03-30 Impact factor: 14.919