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5 results on '"Viswanathan, A. (Anand)"'

1. Asymptomatic Cerebral Small Vessel Disease: Insights from Population-Based Studies

Author

Das, A.S., Regenhardt, R.W., Vernooij, M.W. (Meike), Blacker, D, Charidimou, A, Viswanathan, A. (Anand), Das, A.S., Regenhardt, R.W., Vernooij, M.W. (Meike), Blacker, D, Charidimou, A, and Viswanathan, A. (Anand)

Abstract

Cerebral small vessel disease (CSVD) is a common group of neurological conditions that confer a significant burden of morbidity and mortality worldwide. In most cases, CSVD is only recognized in its advanced stages once its symptomatic sequelae develop. However, its significance in asymptomatic healthy populations remains poorly defined. In population-based studies of presumed healthy elderly individuals, CSVD neuroimaging markers including white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, cortical superficial siderosis, and cerebral microinfarcts are frequently detected. While the presence of these imaging markers may reflect unique mechanisms at play, there are likely shared pathways underlying CSVD. Herein, we aim to assess the etiology and significance of these individual biomarkers by focusing in asymptomatic populations at an epidemiological level

Published
2019
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2. Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma

Author

King, R. (Richard), Struebing, F.L., Li, Y. (Yuwen), Wang, J., Koch, A.A., Bailey, JNC, Gharahkhani, P, Macgregor, S., Allingham, R.R. (R Rand), Hauser, M.A. (Michael), Wiggs, J.L. (Janey), Geisert, E.E., Allingham, R., Brilliant, M., Budenz, D., Bailey, J.C., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J.L. (Jonathan), Hark, L., Hauser, M., Igo, R., Kang, J.H. (Jae), Kraft, P. (Peter), Lee, R. (R.) van der, Lichter, P. (Peter), Liu, Y. (Yu), Moroi, S., Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A., Rhee, D., Richards, J. (John), Ritch, R., Schuman, J., Scott, W.K. (William), Singh, K, Sit, A., Vollrath, D., Weinreb, RN, Wollstein, G., Zack, D., Aung, T. (Tin), Burdon, K.P. (Kathryn), Cheng, C-Y. (Ching-Yu), Bailey, J.N.C., Craig, J.E. (Jamie), Cree, A.J. (Angela), Hammond, C.J. (Christopher), Hewit, A.W. (Alex), Höhn, R., Hysi, P.G. (Pirro), Gonzalez, A.I., Jonas, J., Khawaja, A, Khor, C.C., Klaver, C.C.W. (Caroline), Pasutto, F. (Francesca), Mackey, D., Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C., Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Duijn, C.M., Viswanathan, A. (Anand), Vitart, V. (Veronique), Wojciechowski, R. (Robert), Wong, T., Young, T.L. (Terri), Zeller, T. (Tanja), King, R. (Richard), Struebing, F.L., Li, Y. (Yuwen), Wang, J., Koch, A.A., Bailey, JNC, Gharahkhani, P, Macgregor, S., Allingham, R.R. (R Rand), Hauser, M.A. (Michael), Wiggs, J.L. (Janey), Geisert, E.E., Allingham, R., Brilliant, M., Budenz, D., Bailey, J.C., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J.L. (Jonathan), Hark, L., Hauser, M., Igo, R., Kang, J.H. (Jae), Kraft, P. (Peter), Lee, R. (R.) van der, Lichter, P. (Peter), Liu, Y. (Yu), Moroi, S., Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A., Rhee, D., Richards, J. (John), Ritch, R., Schuman, J., Scott, W.K. (William), Singh, K, Sit, A., Vollrath, D., Weinreb, RN, Wollstein, G., Zack, D., Aung, T. (Tin), Burdon, K.P. (Kathryn), Cheng, C-Y. (Ching-Yu), Bailey, J.N.C., Craig, J.E. (Jamie), Cree, A.J. (Angela), Hammond, C.J. (Christopher), Hewit, A.W. (Alex), Höhn, R., Hysi, P.G. (Pirro), Gonzalez, A.I., Jonas, J., Khawaja, A, Khor, C.C., Klaver, C.C.W. (Caroline), Pasutto, F. (Francesca), Mackey, D., Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C., Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Duijn, C.M., Viswanathan, A. (Anand), Vitart, V. (Veronique), Wojciechowski, R. (Robert), Wong, T., Young, T.L. (Terri), and Zeller, T. (Tanja)

Abstract

Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60–100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10−6 for SNP rs7631

Published
2018
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3. Clinical significance of cerebral microbleeds on MRI

Author

Charidimou, A. (Andreas), Shams, S. (Sara), Romero, J.R. (Jose Rafael), Ding, J. (Jie), Veltkamp, R. (Roland), Horstmann, S. (Solveig), Eiriksdottir, G. (Gudny), Buchem, M.A. (Mark) van, Gudnason, V. (Vilmundur), Himali, J.J. (Jayandra), Gurol, M.E. (Edip), Viswanathan, A. (Anand), Imaizumi, T. (Toshio), Vernooij, M.W. (Meike), Seshadri, S. (Sudha), Greenberg, S.M. (Steven), Benavente, O.R. (Oscar), Launer, L.J. (Lenore), Shoamanesh, A. (Ashkan), Charidimou, A. (Andreas), Shams, S. (Sara), Romero, J.R. (Jose Rafael), Ding, J. (Jie), Veltkamp, R. (Roland), Horstmann, S. (Solveig), Eiriksdottir, G. (Gudny), Buchem, M.A. (Mark) van, Gudnason, V. (Vilmundur), Himali, J.J. (Jayandra), Gurol, M.E. (Edip), Viswanathan, A. (Anand), Imaizumi, T. (Toshio), Vernooij, M.W. (Meike), Seshadri, S. (Sudha), Greenberg, S.M. (Steven), Benavente, O.R. (Oscar), Launer, L.J. (Lenore), and Shoamanesh, A. (Ashkan)

Abstract

__Background:__ Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies. __Methods:__ Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results: We identified 31 cohorts (n = 20,368): 19 ischemic stroke/TIA (n = 7672), 4 memory clinic (n = 1957), 3 high risk elderly (n = 1458) and 5 population-based cohorts (n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. __Conclusions:__ Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supp

Published
2018
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4. Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease

Author

De Guio, F. (François), Jouvent, E. (Eric), Biessels, G.J. (Geert Jan), Black, S.E. (Sandra), Brayne, C. (Carol), Chen, C. (Christopher), Cordonnier, C. (Charlotte), Leeuw, H.F. (Frank) de, Kubisch, C. (Christian), Doubal, F. (Fergus), Duering, M. (Marco), Dufouil, C. (Carole), Duzel, E. (Emrah), Fazekas, F. (Franz), Hachinski, V. (Vladimir), Ikram, M.K. (Kamran), Linn, J. (Jennifer), Matthews, P.M. (P.), Mazoyer, B. (Bernard), Mok, V. (Vincent), Norrving, B. (Bo), O'Brien, J.T. (John T.), Pantoni, L. (Leonardo), Ropele, S. (Stefan), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Seshadri, S. (Sudha), Smith, E.E. (Eric), Sposato, L.A. (Luciano A), Stephan, B.C.M., Swartz, R.H. (Richard H.), Tzourio, C. (Christophe), Buchem, M.A. (Mark) van, Lugt, A. (Aad) van der, Oostenbrugge, R.J. (Robert) van, Vernooij, M.W. (Meike), Viswanathan, A. (Anand), Werring, D.J. (David), Wollenweber, F. (Frank), Wardlaw, J.M. (J.), Chabriat, H. (Hugues), De Guio, F. (François), Jouvent, E. (Eric), Biessels, G.J. (Geert Jan), Black, S.E. (Sandra), Brayne, C. (Carol), Chen, C. (Christopher), Cordonnier, C. (Charlotte), Leeuw, H.F. (Frank) de, Kubisch, C. (Christian), Doubal, F. (Fergus), Duering, M. (Marco), Dufouil, C. (Carole), Duzel, E. (Emrah), Fazekas, F. (Franz), Hachinski, V. (Vladimir), Ikram, M.K. (Kamran), Linn, J. (Jennifer), Matthews, P.M. (P.), Mazoyer, B. (Bernard), Mok, V. (Vincent), Norrving, B. (Bo), O'Brien, J.T. (John T.), Pantoni, L. (Leonardo), Ropele, S. (Stefan), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Seshadri, S. (Sudha), Smith, E.E. (Eric), Sposato, L.A. (Luciano A), Stephan, B.C.M., Swartz, R.H. (Richard H.), Tzourio, C. (Christophe), Buchem, M.A. (Mark) van, Lugt, A. (Aad) van der, Oostenbrugge, R.J. (Robert) van, Vernooij, M.W. (Meike), Viswanathan, A. (Anand), Werring, D.J. (David), Wollenweber, F. (Frank), Wardlaw, J.M. (J.), and Chabriat, H. (Hugues)

Abstract

Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.

Published
2016
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5. Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis

Author

Holliday, E.G. (Elizabeth), Smith, A.V. (Davey), Cornes, B.K. (Belinda), Buitendijk, G.H.S. (Gabrielle), Jensen, R.A. (Richard), Sim, X. (Xueling), Aspelund, T. (Thor), Aung, T. (Tin), Baird, P.N. (Paul), Boerwinkle, E.A. (Eric), Cheng, C-Y. (Ching-Yu), Duijn, C.M. (Cornelia) van, Eiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hewit, A.W. (Alex), Inouye, M. (Michael), Jonasson, F. (Fridbert), Klein, B.E.K. (Barbara), Launer, L.J. (Lenore), Li, X. (Xiaohui), Liew, G. (Gerald), Lumley, T. (Thomas), McElduff, P. (Patrick), McKnight, B. (Barbara), Mitchell, P. (Paul), Psaty, B.M. (Bruce), Rochtchina, E. (Elena), Rotter, J.I. (Jerome), Scott, R.J. (Rodney), Tay, W.-T. (Wan-Ting), Taylor, K. (Kent), Teo, Y.Y. (Yik Ying), Uitterlinden, A.G. (André), Viswanathan, A. (Anand), Xie, S. (Sophia), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Tai, E.S. (Shyong), Siscovick, D.S. (David), Klein, R. (Ronald), Cotch, M.F. (Mary Frances), Wong, T.Y. (Tien Yin), Attia, J. (John), Wang, J.J. (Jie Jin), Holliday, E.G. (Elizabeth), Smith, A.V. (Davey), Cornes, B.K. (Belinda), Buitendijk, G.H.S. (Gabrielle), Jensen, R.A. (Richard), Sim, X. (Xueling), Aspelund, T. (Thor), Aung, T. (Tin), Baird, P.N. (Paul), Boerwinkle, E.A. (Eric), Cheng, C-Y. (Ching-Yu), Duijn, C.M. (Cornelia) van, Eiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hewit, A.W. (Alex), Inouye, M. (Michael), Jonasson, F. (Fridbert), Klein, B.E.K. (Barbara), Launer, L.J. (Lenore), Li, X. (Xiaohui), Liew, G. (Gerald), Lumley, T. (Thomas), McElduff, P. (Patrick), McKnight, B. (Barbara), Mitchell, P. (Paul), Psaty, B.M. (Bruce), Rochtchina, E. (Elena), Rotter, J.I. (Jerome), Scott, R.J. (Rodney), Tay, W.-T. (Wan-Ting), Taylor, K. (Kent), Teo, Y.Y. (Yik Ying), Uitterlinden, A.G. (André), Viswanathan, A. (Anand), Xie, S. (Sophia), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Tai, E.S. (Shyong), Siscovick, D.S. (David), Klein, R. (Ronald), Cotch, M.F. (Mary Frances), Wong, T.Y. (Tien Yin), Attia, J. (John), and Wang, J.J. (Jie Jin)

Published
2013
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