Refine
Has Fulltext
- yes (3)
Is part of the Bibliography
- yes (3)
Document Type
- Journal article (3)
Language
- English (3)
Keywords
- association (1)
- beaver-dam eye (1)
- central corneal thickness (1)
- expression (1)
- genome-wide scan (1)
- goldmann applanation tonometer (1)
- identification (1)
- onset (1)
- population (1)
- to-disc ratio (1)
Institute
Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p = 1.4 x 10\(^{-8}\)), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6 x 10\(^{-8}\)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p = 2.4 x 10\(^{-2}\) for rs11656696 and p = 9.1 x 10\(^{-4}\) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.
“Everything changes and nothing stands still” (Heraclitus). Here we review three major improvements to freshwater aquatic ecosystem models — and ecological models in general — as water quality scenario analysis tools towards a sustainable future. To tackle the rapid and deeply connected dynamics characteristic of the Anthropocene, we argue for the inclusion of eco-evolutionary, novel ecosystem and social-ecological dynamics. These dynamics arise from adaptive responses in organisms and ecosystems to global environmental change and act at different integration levels and different time scales. We provide reasons and means to incorporate each improvement into aquatic ecosystem models. Throughout this study we refer to Lake Victoria as a microcosm of the evolving novel social-ecological systems of the Anthropocene. The Lake Victoria case clearly shows how interlinked eco-evolutionary, novel ecosystem and social-ecological dynamics are, and demonstrates the need for transdisciplinary research approaches towards global sustainability.
The aim of the present paper is to clarify the role of extreme order statistics in general statistical models. This is done within the general setup of statistical experiments in LeCam's sense. Under the assumption of monotone likelihood ratios, we prove that a sequence of experiments is asymptotically Gaussian if, and only if, a fixed number of extremes asymptotically does not contain any information. In other words: A fixed number of extremes asymptotically contains information iff the Poisson part of the limit experiment is non-trivial. Suggested by this result, we propose a new extreme value model given by local alternatives. The local structure is described by introducing the space of extreme value tangents. It turns out that under local alternatives a new class of extreme value distributions appears as limit distributions. Moreover, explicit representations of the Poisson limit experiments via Poisson point processes are found. As a concrete example nonparametric tests for Frechet type distributions against stochastically larger alternatives are treated. We find asymptotically optimal tests within certain threshold models.