Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10-10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10-9). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10-14, OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10-14, OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. © 2011 Nature America, Inc. All rights reserved.

An extravariation model for improving confidence intervals of population size estimates from removal data

We propose a new model for estimating the size of a population from successive catches taken during a removal experiment. The data from these experiments often have excessive variation, known as overdispersion, as compared with that predicted by the multinomial model. The new model allows catchability to vary randomly among samplings, which accounts for overdispersion. When the catchability is assumed to have a beta distribution, the likelihood function, which is refered to as beta-multinomial, is derived, and hence the maximum likelihood estimates can be evaluated. Simulations show that in the presence of extravariation in the data, the confidence intervals have been substantially underestimated in previous models (Leslie-DeLury, Moran) and that the new model provides more reliable confidence intervals. The performance of these methods was also demonstrated using two real data sets: one with overdispersion, from smallmouth bass (Micropterus dolomieu), and the other without overdispersion, from rat (Rattus rattus).