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Search Results: 1 - 10 of 227603 matches for " Johannes R. Vingerling "
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Cholesterol-Lowering Drugs and Incident Open-Angle Glaucoma: A Population-Based Cohort Study
Michael W. Marcus, Rogier P. H. M. Müskens, Wishal D. Ramdas, Roger C. W. Wolfs, Paulus T. V. M. De Jong, Johannes R. Vingerling, Albert Hofman, Bruno H. Stricker, Nomdo M. Jansonius
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029724
Abstract: Background Open-angle glaucoma (OAG) is a progressive neurodegenerative disease that may lead to blindness. An elevated intraocular pressure (IOP) is its major risk factor. OAG treatment is currently exclusively directed towards the lowering of the IOP. IOP lowering does not prevent disease progression in all patients and thus other treatment modalities are needed. Earlier studies reported cholesterol-lowering drugs to have neuroprotective properties. The aim of this study was to determine the associations between the use of cholesterol-lowering drugs and incident OAG. Methodology/Principal Findings Participants in a prospective population-based cohort study underwent ophthalmic examinations, including IOP measurements and perimetry, at baseline and follow-up. The use of statins and non-statin cholesterol-lowering drugs was monitored continuously during the study. Associations between the use of cholesterol-lowering drugs and incident OAG were analyzed with Cox regression; associations between cholesterol-lowering drugs and IOP at follow-up were analyzed with multiple linear regression. During a mean follow-up of 9.8 years, 108 of 3939 eligible participants (2.7%) developed OAG. The hazard ratio for statin use was 0.54 (95% confidence interval 0.31–0.96; P = 0.034) and for non-statin cholesterol-lowering drugs 2.07 (0.81–5.33; P = 0.13). The effect of statins was more pronounced with prolonged use (hazard ratio 0.89 [0.41–1.94; P = 0.77] for use two years or less; 0.46 [0.23–0.94; P = 0.033] for use more than two years; P-value for trend 0.10). The analyzes were adjusted for age and gender, baseline IOP and IOP-lowering treatment, the family history of glaucoma, and myopia. There was no effect of statins on the IOP. Conclusions/Significance Long-term use of statins appears to be associated with a reduced risk of OAG. The observed effect was independent of the IOP. These findings are in line with the idea that statins have neuroprotective properties and may open a way to a new OAG treatment modality.
The ERCC6 Gene and Age-Related Macular Degeneration
Dominique C. Baas,Dominiek D. Despriet,Theo G. M. F. Gorgels,Julie Bergeron-Sawitzke,André G. Uitterlinden,Albert Hofman,Cornelia M. van Duijn,Joanna E. Merriam,R. Theodore Smith,Gaetano R. Barile,Jacoline B. ten Brink,Johannes R. Vingerling,Caroline C. W. Klaver,Rando Allikmets,Michael Dean,Arthur A. B. Bergen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013786
Abstract: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS.
Digital Quantification of Human Eye Color Highlights Genetic Association of Three New Loci
Fan Liu,Andreas Wollstein,Pirro G. Hysi,Georgina A. Ankra-Badu,Timothy D. Spector,Daniel Park,Gu Zhu,Mats Larsson,David L. Duffy,Grant W. Montgomery,David A. Mackey,Susan Walsh,Oscar Lao,Albert Hofman,Fernando Rivadeneira,Johannes R. Vingerling,André G. Uitterlinden,Nicholas G. Martin,Christopher J. Hammond,Manfred Kayser
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1000934
Abstract: Previous studies have successfully identified genetic variants in several genes associated with human iris (eye) color; however, they all used simplified categorical trait information. Here, we quantified continuous eye color variation into hue and saturation values using high-resolution digital full-eye photographs and conducted a genome-wide association study on 5,951 Dutch Europeans from the Rotterdam Study. Three new regions, 1q42.3, 17q25.3, and 21q22.13, were highlighted meeting the criterion for genome-wide statistically significant association. The latter two loci were replicated in 2,261 individuals from the UK and in 1,282 from Australia. The LYST gene at 1q42.3 and the DSCR9 gene at 21q22.13 serve as promising functional candidates. A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study. Over all our data exemplify that fine phenotyping is a useful strategy for finding genes involved in human complex traits.
A Genome-Wide Association Study of Optic Disc Parameters
Wishal D. Ramdas equal contributor,Leonieke M. E. van Koolwijk equal contributor,M. Kamran Ikram equal contributor,Nomdo M. Jansonius,Paulus T. V. M. de Jong,Arthur A. B. Bergen,Aaron Isaacs,Najaf Amin,Yurii S. Aulchenko,Roger C. W. Wolfs,Albert Hofman,Fernando Rivadeneira,Ben A. Oostra,Andre G. Uitterlinden,Pirro Hysi,Christopher J. Hammond,Hans G. Lemij,Johannes R. Vingerling ,Caroline C. W. Klaver equal contributor,Cornelia M. van Duijn equal contributor
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1000978
Abstract: The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72×10?19) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67×10?33) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15×10?11) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93×10?10) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.
Genetic Loci for Retinal Arteriolar Microcirculation
Xueling Sim, Richard A. Jensen, M. Kamran Ikram, Mary Frances Cotch, Xiaohui Li, Stuart MacGregor, Jing Xie, Albert Vernon Smith, Eric Boerwinkle, Paul Mitchell, Ronald Klein, Barbara E. K. Klein, Nicole L. Glazer, Thomas Lumley, Barbara McKnight, Bruce M. Psaty, Paulus T. V. M. de Jong, Albert Hofman, Fernando Rivadeneira, Andre G. Uitterlinden, Cornelia M. van Duijn, Thor Aspelund, Gudny Eiriksdottir, Tamara B. Harris, Fridbert Jonasson, Lenore J. Launer, The Wellcome Trust Case Control Consortium 2 , John Attia, Paul N. Baird, Stephen Harrap, Elizabeth G. Holliday, Michael Inouye, Elena Rochtchina, Rodney J. Scott, Ananth Viswanathan, Global BPGen Consortium , Guo Li, Nicholas L. Smith, Kerri L. Wiggins, Jane Z. Kuo, Kent D. Taylor, Alex W. Hewitt, Nicholas G. Martin, Grant W. Montgomery, Cong Sun, Terri L. Young, David A. Mackey, Natalie R. van Zuydam, Alex S. F. Doney, Colin N. A. Palmer, Andrew D. Morris, Jerome I. Rotter, E. Shyong Tai, Vilmundur Gudnason, Johannes R. Vingerling, David S. Siscovick, Jie Jin Wang, Tien Y. Wong
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065804
Abstract: Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10?8. This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10?12 in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.
Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma
Leonieke M. E. van Koolwijk equal contributor,Wishal D. Ramdas equal contributor,M. Kamran Ikram,Nomdo M. Jansonius,Francesca Pasutto,Pirro G. Hysi,Stuart Macgregor,Sarah F. Janssen,Alex W. Hewitt,Ananth C. Viswanathan,Jacoline B. ten Brink,S. Mohsen Hosseini,Najaf Amin,Dominiek D. G. Despriet,Jacqueline J. M. Willemse-Assink,Rogier Kramer,Fernando Rivadeneira,Maksim Struchalin,Yurii S. Aulchenko,Nicole Weisschuh,Matthias Zenkel,Christian Y. Mardin,Eugen Gramer,Ulrich Welge-Lüssen,Grant W. Montgomery,Francis Carbonaro,Terri L. Young,The DCCT/EDIC Research Group,Céline Bellenguez,Peter McGuffin,Paul J. Foster,Fotis Topouzis,Paul Mitchell,Jie Jin Wang,Tien Y. Wong,Monika A. Czudowska,Albert Hofman,Andre G. Uitterlinden,Roger C. W. Wolfs,Paulus T. V. M. de Jong,Ben A. Oostra,Andrew D. Paterson,Wellcome Trust Case Control Consortium 2,David A. Mackey,Arthur A. B. Bergen,André Reis,Christopher J. Hammond,Johannes R. Vingerling,Hans G. Lemij,Caroline C. W. Klaver,Cornelia M. van Duijn
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002611
Abstract: 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 = 1.4×10?8), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6×10?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 = 2.4×10?2 for rs11656696 and p = 9.1×10?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.
Effective intrinsic linear properties of laminar piezoelectric composites and simple ferroelectric domain structures
Johannes R?del
Physics , 2005,
Abstract: The effective properties of piezoelectric laminates have been analyzed, based on the calculation of internal fields and making use of a simple matrix manipulation method. The results are expressed in a compact notation which is convenient for numerical implementation and at the same time suitable for further analytical treatments. A detailed analysis of fully compatible ferroelectric domain structures shows, that the results for arbitrary piezoelectric laminates can be further simplified and specific property relationships for rank-1 laminates of tetragonal and rhombohedral crystals are derived. The method is finally applied to the analysis of various hierarchical domain structures. Detailed orientation relationships between the particular domains in some important domain pattern are given to make these structures accessible for the presented method. Some numerical results for tetragonal barium titanate illustrate the effects of different domain arrangements on the effective properties.
Micro-mechanics of multi-phase ferroelectric domain structures
Johannes R?del
Physics , 2006, DOI: 10.1117/12.659041
Abstract: High-strain piezoelectric materials are often ceramics with a complicated constitution. In particular, PZT is used with compositions near to a so-called morphotropic phase boundary, where not only different variants of the same phase (domains), but different phases may coexist. Micro-mechanical models for ferroelectric ceramics would be much more realistic, if these effects could be incorporated. In this paper, we consider the conditions of mechanical and electrical compatibility of ferroelectric domain structures. We are able to address the question of coexistence of different crystallographic phases within the very same crystallite. In general, the spontaneous strain and spontaneous polarization of different phases are not compatible. The numerical analysis of the derived relationships are susceptible to the crystallographic description of the phases in question. In this presentation, a simple analysis and analytical, composition dependent fit of strain and polarization of PZT at room temperature for available data are used. The outlined approach can be used to model the overall behavior of multi-variant and multi-phase crystallites with certain, simplified geometrical arrangements of the constituents.
A Combinatorial Classification of Postcritically Fixed Newton Maps
Johannes Rückert
Mathematics , 2007,
Abstract: We give a combinatorial classification for the class of postcritically fixed Newton maps of polynomials and indicate potential for extensions. As our main tool, we show that for a large class of Newton maps that includes all hyperbolic ones, every component of the basin of an attracting fixed point can be connected to infinity through a finite chain of such components.
On rate optimal local estimation in functional linear model
J. Johannes,R. Schenk
Mathematics , 2009,
Abstract: We consider the estimation of the value of a linear functional of the slope parameter in functional linear regression, where scalar responses are modeled in dependence of random functions. The theory in this paper covers in particular point-wise estimation as well as the estimation of weighted averages of the slope parameter. We propose a plug-in estimator which is based on a dimension reduction technique and additional thresholding. It is shown that this estimator is consistent under mild assumptions. We derive a lower bound for the maximal mean squared error of any estimator over a certain ellipsoid of slope parameters and a certain class of covariance operators associated with the regressor. It is shown that the proposed estimator attains this lower bound up to a constant and hence it is minimax optimal. Our results are appropriate to discuss a wide range of possible regressors, slope parameters and functionals. They are illustrated by considering the point-wise estimation of the slope parameter or its derivatives and its average value over a given interval.
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