Author: "Van Es, Michael A." - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Van Es, Michael A."' showing total 691 results

Start Over Author "Van Es, Michael A."

691 results on '"Van Es, Michael A."'

201. Prospective natural history study of ALS clinical characteristics and biomarkers.

Author: Cammack, Alexander J., Atassi, Nazem, Hyman, Theodore, van den Berg, Leonard H., Harms, Matthew, Baloh, Robert H., Brown, Robert H., van Es, Michael A., Veldink, Jan H., de Vries, Balint S., Rothstein, Jeffrey D., Drain, Caroline, Jockel-Balsarotti, Jennifer, Malcolm, Amber, Boodram, Sonia, Salter, Amber, Wightman, Nicholas, Hong Yu, Sherman, Alexander V., and Esparza, Thomas J.
Published: 2019
Full Text: View/download PDF

202. Cognitive and behavioural changes in PLS and PMA: challenging the concept of restricted phenotypes.

Author: de Vries, Bálint S., Rustemeijer, Laura M. M., Bakker, Leonhard A., Schröder, Carin D., Veldink, Jan H., van den Berg, Leonard H., Nijboer, Tanja C. W., and van Es, Michael A.
Subjects: FRONTOTEMPORAL lobar degeneration, APHASIA, SPINAL muscular atrophy, FAMILIAL spastic paraplegia
Published: 2019
Full Text: View/download PDF

203. "ALS reversals": demographics, disease characteristics, treatments, and co-morbidities.

Author: Harrison, Daniel, Mehta, Paul, van Es, Michael A., Stommel, Elijah, Drory, Vivian E., Nefussy, Beatrice, van den Berg, Leonard H., Crayle, Jesse, Bedlack, Richard, and the Pooled Resource Open-Access ALS Clinical Trials Consortium
Subjects: COMORBIDITY, AMYOTROPHIC lateral sclerosis, DISEASE progression, DISEASE prevalence, MYASTHENIA gravis
Abstract: Objective: To identify differences in demographics, disease characteristics, treatments, and co-morbidities between patients with "amyotrophic lateral sclerosis (ALS) reversals" and those with typically progressive ALS. Methods: Cases of possible ALS reversals were found in prior publications, in the Duke ALS clinic, through self-referral or referral from other Neurologists, and on the internet. Of 89 possible reversals identified, 36 cases were included because chart or literature review confirmed their diagnosis and a robust, sustained improvement in at least one objective measure. Controls were participants in the Pooled Resource Open-Access ALS Clinical Trials database and the National ALS Registry. Cases and controls were compared using descriptive statistics. Results: ALS reversals were more likely to be male, have limb onset disease, and initially progress faster. The prevalences of myasthenia gravis (MG) and purely lower motor neuron disease in cases were higher than estimates of these prevalences in the general population. The odds of taking curcumin, luteolin, cannabidiol, azathioprine, copper, glutathione, vitamin D, and fish oil were greater for cases than controls. Conclusions: When compared to patients with typically progressive ALS, patients with reversals differed in their demographics, disease characteristics, and treatments. While some of these patients may have had a rare antibody-mediated ALS mimicker, such as atypical myasthenia gravis, details of their exams, EMGs and family histories argue that this was unlikely. Instead, our data suggest that ALS reversals warrant evaluation for mechanisms of disease resistance and that treatments associated with multiple ALS reversals deserve further study. [ABSTRACT FROM AUTHOR]
Published: 2018
Full Text: View/download PDF

204. NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

Author: Kenna, Kevin P., van Doormaal, Perry T. C., Dekker, Annelot M., Ticozzi, Nicola, Kenna, Brendan J., Diekstra, Frank P., van Rheenen, Wouter, van Eijk, Kristel R., Jones, Ashley R., Keaglel, Pamela, Shatunov, Aleksey, Sproviero, William, Smiths, Bradley N., van Es, Michael A., Topps, Simon D., Kenna, Aoife, Miller, Jack W., Fallini, Claudia, Tiloca, Cinzia, McLaughlin, Russell L., Vance, Caroline, Troakes, Claire, Colombrita, Claudia, Mora, Gabriele, Calvo, Andrea, Verde, Federico, Al-Sarraj, Safa, King, Andrew, Calini, Daniela, de Belleroche, Jacqueline, Baas, Frank, van der Kooi, Anneke J., de Visser, Marianne, ten Asbroek, Anneloor L. M. A., Sapp, Peter C., McKenna-Yasek, Diane, Polak, Meraida, Asress, Seneshaw, Luis Munoz-Blanco, Jose, Strom, Tim M., Meitinger, Thomas, Morrison, Karen E., Lauria, Giuseppe, Williams, Kelly L., Leigh, P. Nigel, Nicholson, Garth A., Blair, Ian P., Leblond, Claire S., Dion, Patrick A., Rouleau, Guy A., Pall, Hardev, Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Taroni, Franco, Boylan, Kevin B., Van Blitterswijk, Marka, Rademakers, Rosa, Esteban-Perez, Jesus, Garcia-Redondo, Alberto, Van Damme, Phillip, Robberecht, Wim, Chio, Adrian, Gellera, Cinzia, Drepper, Carsten, Sendtner, Michael, Ratti, Antonia, Glass, Jonathan D., Mora, Jesus S., Basak, Nazli A., Hardiman, Orla, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Brown, Robert H., Jr., Al-Chalabi, Ammar, Silani, Vincenzo, Shaw, Christopher E., van den Berg, Leonard H., Veldink, Jan H., Landers, John E., D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P., Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Soraru, Gianni, Kenna, Kevin P., van Doormaal, Perry T. C., Dekker, Annelot M., Ticozzi, Nicola, Kenna, Brendan J., Diekstra, Frank P., van Rheenen, Wouter, van Eijk, Kristel R., Jones, Ashley R., Keaglel, Pamela, Shatunov, Aleksey, Sproviero, William, Smiths, Bradley N., van Es, Michael A., Topps, Simon D., Kenna, Aoife, Miller, Jack W., Fallini, Claudia, Tiloca, Cinzia, McLaughlin, Russell L., Vance, Caroline, Troakes, Claire, Colombrita, Claudia, Mora, Gabriele, Calvo, Andrea, Verde, Federico, Al-Sarraj, Safa, King, Andrew, Calini, Daniela, de Belleroche, Jacqueline, Baas, Frank, van der Kooi, Anneke J., de Visser, Marianne, ten Asbroek, Anneloor L. M. A., Sapp, Peter C., McKenna-Yasek, Diane, Polak, Meraida, Asress, Seneshaw, Luis Munoz-Blanco, Jose, Strom, Tim M., Meitinger, Thomas, Morrison, Karen E., Lauria, Giuseppe, Williams, Kelly L., Leigh, P. Nigel, Nicholson, Garth A., Blair, Ian P., Leblond, Claire S., Dion, Patrick A., Rouleau, Guy A., Pall, Hardev, Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Taroni, Franco, Boylan, Kevin B., Van Blitterswijk, Marka, Rademakers, Rosa, Esteban-Perez, Jesus, Garcia-Redondo, Alberto, Van Damme, Phillip, Robberecht, Wim, Chio, Adrian, Gellera, Cinzia, Drepper, Carsten, Sendtner, Michael, Ratti, Antonia, Glass, Jonathan D., Mora, Jesus S., Basak, Nazli A., Hardiman, Orla, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Brown, Robert H., Jr., Al-Chalabi, Ammar, Silani, Vincenzo, Shaw, Christopher E., van den Berg, Leonard H., Veldink, Jan H., Landers, John E., D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P., Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, and Soraru, Gianni
Abstract: To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.
Published: 2016
Full Text: View/download PDF

205. Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis

Author: Fogh, Isabella, Lin, Kuang, Tiloca, Cinzia, Rooney, James, Gellera, Cinzia, Diekstra, Frank P., Ratti, Antonia, Shatunov, Aleksey, van Es, Michael A., Proitsi, Petroula, Jones, Ashley, Sproviero, William, Chio, Adriano, McLaughlin, Russell Lewis, Soraru, Gianni, Corrado, Lucia, Stahl, Daniel, Del Bo, Roberto, Cereda, Cristina, Castellotti, Barbara, Glass, Jonathan D., Newhouse, Steven, Dobson, Richard, Smith, Bradley N., Topp, Simon, van Rheenen, Wouter, Meininger, Vincent, Melki, Judith, Morrison, Karen E., Shaw, Pamela J., Leigh, P. Nigel, Andersen, Peter M., Comi, Giacomo P., Ticozzi, Nicola, Mazzini, Letizia, D'Alfonso, Sandra, Traynor, Bryan J., Van Damme, Philip, Robberecht, Wim, Brown, Robert H., Landers, John E., Hardiman, Orla, Lewis, Cathryn M., van den Berg, Leonard H., Shaw, Christopher E., Veldink, Jan H., Silani, Vincenzo, Al-Chalabi, Ammar, Powell, John, Fogh, Isabella, Lin, Kuang, Tiloca, Cinzia, Rooney, James, Gellera, Cinzia, Diekstra, Frank P., Ratti, Antonia, Shatunov, Aleksey, van Es, Michael A., Proitsi, Petroula, Jones, Ashley, Sproviero, William, Chio, Adriano, McLaughlin, Russell Lewis, Soraru, Gianni, Corrado, Lucia, Stahl, Daniel, Del Bo, Roberto, Cereda, Cristina, Castellotti, Barbara, Glass, Jonathan D., Newhouse, Steven, Dobson, Richard, Smith, Bradley N., Topp, Simon, van Rheenen, Wouter, Meininger, Vincent, Melki, Judith, Morrison, Karen E., Shaw, Pamela J., Leigh, P. Nigel, Andersen, Peter M., Comi, Giacomo P., Ticozzi, Nicola, Mazzini, Letizia, D'Alfonso, Sandra, Traynor, Bryan J., Van Damme, Philip, Robberecht, Wim, Brown, Robert H., Landers, John E., Hardiman, Orla, Lewis, Cathryn M., van den Berg, Leonard H., Shaw, Christopher E., Veldink, Jan H., Silani, Vincenzo, Al-Chalabi, Ammar, and Powell, John
Abstract: IMPORTANCE Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset. OBJECTIVE To identify gene variants influencing survival in ALS. DESIGN, SETTING, AND PARTICIPANTS This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015. MAIN OUTCOMES AND MEASURES Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed bymeta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis. RESULTS Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 x 10(-9)) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 x 10(-8)). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 x 10(-9)), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208 CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 x 10(-8)), corresponding to a 4-month reduction in survival compared with TT carriers. CONCLUSI
Published: 2016
Full Text: View/download PDF

206. Amyotrofische laterale sclerose, een heterogene ziekte

Author: van Es, Michael A, Kruitwagen-van Reenen, Esther T., Schröder, Carin D., Pasterkamp, R. J Jeroen, Veldink, Jan H., Van Den Berg, Leonard H., van Es, Michael A, Kruitwagen-van Reenen, Esther T., Schröder, Carin D., Pasterkamp, R. J Jeroen, Veldink, Jan H., and Van Den Berg, Leonard H.
Published: 2016

207. Amyotrofische laterale sclerose, een heterogene ziekte

Author: Projectafdeling ALS, Brain, RF&S Team 1 Medisch, TN groep Pasterkamp, Regenerative Medicine and Stem Cells, Neurogenetica, ZL Neuromusculaire Ziekten Medisch, van Es, Michael A, Kruitwagen-van Reenen, Esther T., Schröder, Carin D., Pasterkamp, R. J Jeroen, Veldink, Jan H., Van Den Berg, Leonard H., Projectafdeling ALS, Brain, RF&S Team 1 Medisch, TN groep Pasterkamp, Regenerative Medicine and Stem Cells, Neurogenetica, ZL Neuromusculaire Ziekten Medisch, van Es, Michael A, Kruitwagen-van Reenen, Esther T., Schröder, Carin D., Pasterkamp, R. J Jeroen, Veldink, Jan H., and Van Den Berg, Leonard H.
Published: 2016

208. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

Author: Opleiding Neurologie, Brain, Neurogenetica, Projectafdeling ALS, TN groep Pasterkamp, Onderzoek, Circulatory Health, ZL Neuromusculaire Ziekten Medisch, CMM Groep Kaaij, Infection & Immunity, Regenerative Medicine and Stem Cells, van Rheenen, Wouter, Shatunov, Aleksey, Dekker, Annelot M, McLaughlin, Russell L, Diekstra, Frank P, Pulit, Sara L, van der Spek, Rick A A, Võsa, Urmo, de Jong, Simone, Robinson, Matthew R, Yang, Jian, Fogh, Isabella, van Doormaal, Perry Tc, Tazelaar, Gijs H P, Koppers, Max, Blokhuis, Anna M, Sproviero, William, Jones, Ashley R, Kenna, Kevin P, van Eijk, Kristel R, Harschnitz, Oliver, Schellevis, Raymond D, Brands, William J, Medic, Jelena, Menelaou, Androniki, Vajda, Alice, Ticozzi, Nicola, Lin, Kuang, Rogelj, Boris, Vrabec, Katarina, Ravnik-Glavač, Metka, Koritnik, Blaž, Zidar, Janez, Leonardis, Lea, Grošelj, Leja Dolenc, Millecamps, Stéphanie, Salachas, François, Meininger, Vincent, de Carvalho, Mamede, Pinto, Susana, Mora, Jesus S, Rojas-García, Ricardo, Polak, Meraida, Ophoff, Roel A., Blauw, Hylke M, de Bakker, Paul I W, van Es, Michael A, Pasterkamp, R Jeroen, van den Berg, Leonard H, Veldink, Jan H, PARALS Registry, Opleiding Neurologie, Brain, Neurogenetica, Projectafdeling ALS, TN groep Pasterkamp, Onderzoek, Circulatory Health, ZL Neuromusculaire Ziekten Medisch, CMM Groep Kaaij, Infection & Immunity, Regenerative Medicine and Stem Cells, van Rheenen, Wouter, Shatunov, Aleksey, Dekker, Annelot M, McLaughlin, Russell L, Diekstra, Frank P, Pulit, Sara L, van der Spek, Rick A A, Võsa, Urmo, de Jong, Simone, Robinson, Matthew R, Yang, Jian, Fogh, Isabella, van Doormaal, Perry Tc, Tazelaar, Gijs H P, Koppers, Max, Blokhuis, Anna M, Sproviero, William, Jones, Ashley R, Kenna, Kevin P, van Eijk, Kristel R, Harschnitz, Oliver, Schellevis, Raymond D, Brands, William J, Medic, Jelena, Menelaou, Androniki, Vajda, Alice, Ticozzi, Nicola, Lin, Kuang, Rogelj, Boris, Vrabec, Katarina, Ravnik-Glavač, Metka, Koritnik, Blaž, Zidar, Janez, Leonardis, Lea, Grošelj, Leja Dolenc, Millecamps, Stéphanie, Salachas, François, Meininger, Vincent, de Carvalho, Mamede, Pinto, Susana, Mora, Jesus S, Rojas-García, Ricardo, Polak, Meraida, Ophoff, Roel A., Blauw, Hylke M, de Bakker, Paul I W, van Es, Michael A, Pasterkamp, R Jeroen, van den Berg, Leonard H, Veldink, Jan H, and PARALS Registry
Published: 2016

209. Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis

Author: Projectafdeling ALS, Opleiding Neurologie, Neurogenetica, Brain, Regenerative Medicine and Stem Cells, ZL Neuromusculaire Ziekten Medisch, Fogh, Isabella, Lin, Kuang, Tiloca, Cinzia, Rooney, James, Gellera, Cinzia, Diekstra, Frank P, Ratti, Antonia, Shatunov, Aleksey, van Es, Michael A, Proitsi, Petroula, Jones, Ashley, Sproviero, William, Chiò, Adriano, McLaughlin, Russell Lewis, Sorarù, Gianni, Corrado, Lucia, Stahl, Daniel, Del Bo, Roberto, Cereda, Cristina, Castellotti, Barbara, Glass, Jonathan D, Newhouse, Steven, Dobson, Richard, Smith, Bradley N, Topp, Simon, van Rheenen, Wouter, Meininger, Vincent, Melki, Judith, Morrison, Karen E, Shaw, Pamela J, Leigh, P Nigel, Andersen, Peter M, Comi, Giacomo P, Ticozzi, Nicola, Mazzini, Letizia, D'Alfonso, Sandra, Traynor, Bryan J, Van Damme, Philip, Robberecht, Wim, Brown, Robert H, Landers, John E, Hardiman, Orla, Lewis, Cathryn M, van den Berg, Leonard H, Shaw, Christopher E, Veldink, Jan H, Silani, Vincenzo, Al-Chalabi, Ammar, Powell, John, Projectafdeling ALS, Opleiding Neurologie, Neurogenetica, Brain, Regenerative Medicine and Stem Cells, ZL Neuromusculaire Ziekten Medisch, Fogh, Isabella, Lin, Kuang, Tiloca, Cinzia, Rooney, James, Gellera, Cinzia, Diekstra, Frank P, Ratti, Antonia, Shatunov, Aleksey, van Es, Michael A, Proitsi, Petroula, Jones, Ashley, Sproviero, William, Chiò, Adriano, McLaughlin, Russell Lewis, Sorarù, Gianni, Corrado, Lucia, Stahl, Daniel, Del Bo, Roberto, Cereda, Cristina, Castellotti, Barbara, Glass, Jonathan D, Newhouse, Steven, Dobson, Richard, Smith, Bradley N, Topp, Simon, van Rheenen, Wouter, Meininger, Vincent, Melki, Judith, Morrison, Karen E, Shaw, Pamela J, Leigh, P Nigel, Andersen, Peter M, Comi, Giacomo P, Ticozzi, Nicola, Mazzini, Letizia, D'Alfonso, Sandra, Traynor, Bryan J, Van Damme, Philip, Robberecht, Wim, Brown, Robert H, Landers, John E, Hardiman, Orla, Lewis, Cathryn M, van den Berg, Leonard H, Shaw, Christopher E, Veldink, Jan H, Silani, Vincenzo, Al-Chalabi, Ammar, and Powell, John
Published: 2016

210. C9orf72 and UNC13A are shared risk loci for ALS and FTD: a genome-wide meta-analysis

Author: Diekstra, Frank P., Van Deerlin, Vivianna M., van Swieten, John C., Al-Chalabi, Ammar, Ludolph, Albert C., Weishaupt, Jochen H., Hardiman, Orla, Landers, John E., Brown, Robert H., van Es, Michael A., Pasterkamp, R. Jeroen, Koppers, Max, Andersen, Peter M., Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, André G., van Damme, Philip, Melki, Judith, Meininger, Vincent, Shatunov, Aleksey, Shaw, Christopher E., Leigh, P. Nigel, Shaw, Pamela J., Morrison, Karen E., Fogh, Isabella, Chiò, Adriano, Traynor, Bryan J., Czell, David, Weber, Markus, Heutink, Peter, de Bakker, Paul I. W., Silani, Vincenzo, Robberecht, Wim, van den Berg, Leonard H., and Veldink, Jan H.
Subjects: DNA Repeat Expansion, C9orf72 Protein, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Mutation, Humans, Proteins, Nerve Tissue Proteins, Chromosomes, Human, Pair 9, Chromosomes, Human, Pair 19, Polymorphism, Single Nucleotide, Article, Genome-Wide Association Study
Abstract: Substantial clinical, pathological, and genetic overlap exists between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 inclusions have been found in both ALS and FTD cases (FTD-TDP). Recently, a repeat expansion in C9orf72 was identified as the causal variant in a proportion of ALS and FTD cases. We sought to identify additional evidence for a common genetic basis for the spectrum of ALS-FTD.We used published genome-wide association studies data for 4,377 ALS patients and 13,017 controls, and 435 pathology-proven FTD-TDP cases and 1,414 controls for genotype imputation. Data were analyzed in a joint meta-analysis, by replicating topmost associated hits of one disease in the other, and by using a conservative rank products analysis, allocating equal weight to ALS and FTD-TDP sample sizes.Meta-analysis identified 19 genome-wide significant single nucleotide polymorphisms (SNPs) in C9orf72 on chromosome 9p21.2 (lowest p = 2.6 × 10(-12) ) and 1 SNP in UNC13A on chromosome 19p13.11 (p = 1.0 × 10(-11) ) as shared susceptibility loci for ALS and FTD-TDP. Conditioning on the 9p21.2 genotype increased statistical significance at UNC13A. A third signal, on chromosome 8q24.13 at the SPG8 locus coding for strumpellin (p = 3.91 × 10(-7) ) was replicated in an independent cohort of 4,056 ALS patients and 3,958 controls (p = 0.026; combined analysis p = 1.01 × 10(-7) ).We identified common genetic variants in C9orf72, but in addition in UNC13A that are shared between ALS and FTD. UNC13A provides a novel link between ALS and FTD-TDP, and identifies changes in neurotransmitter release and synaptic function as a converging mechanism in the pathogenesis of ALS and FTD-TDP.
Published: 2014

211. No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

Author: Goris, An, van Setten, Jessica, Diekstra, Frank, Ripke, Stephan, Patsopoulos, Nikolaos A, Sawcer, Stephen J, International Multiple Sclerosis Genetics Consortium, van Es, Michael, Australia and New Zealand MS Genetics Consortium, Andersen, Peter M, Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E, Brown, Robert H, Shatunov, Aleksey, Leigh, Nigel, Al-Chalabi, Ammar, Shaw, Christopher E, Traynor, Bryan J, Chiò, Adriano, Restagno, Gabriella, Mora, Gabriele, Ophoff, Roel A, Oksenberg, Jorge R, Van Damme, Philip, Compston, Alastair, Robberecht, Wim, Dubois, Bénédicte, van den Berg, Leonard H, De Jager, Philip L, Veldink, Jan H, and de Bakker, Paul IW
Subjects: Genetics & Heredity, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Human Genome, Neurosciences, Comorbidity, Single Nucleotide, Neurodegenerative, Biological Sciences, Autoimmune Disease, Medical and Health Sciences, International Multiple Sclerosis Genetics Consortium, Brain Disorders, Rare Diseases, Clinical Research, Neurological, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Australia and New Zealand MS Genetics Consortium, Polymorphism, ALS, Aetiology
Abstract: Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.
Published: 2014

212. Association of a Locus in theCAMTA1Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis

Author: Fogh, Isabella, primary, Lin, Kuang, additional, Tiloca, Cinzia, additional, Rooney, James, additional, Gellera, Cinzia, additional, Diekstra, Frank P., additional, Ratti, Antonia, additional, Shatunov, Aleksey, additional, van Es, Michael A., additional, Proitsi, Petroula, additional, Jones, Ashley, additional, Sproviero, William, additional, Chiò, Adriano, additional, McLaughlin, Russell Lewis, additional, Sorarù, Gianni, additional, Corrado, Lucia, additional, Stahl, Daniel, additional, Del Bo, Roberto, additional, Cereda, Cristina, additional, Castellotti, Barbara, additional, Glass, Jonathan D., additional, Newhouse, Steven, additional, Dobson, Richard, additional, Smith, Bradley N., additional, Topp, Simon, additional, van Rheenen, Wouter, additional, Meininger, Vincent, additional, Melki, Judith, additional, Morrison, Karen E., additional, Shaw, Pamela J., additional, Leigh, P. Nigel, additional, Andersen, Peter M., additional, Comi, Giacomo P., additional, Ticozzi, Nicola, additional, Mazzini, Letizia, additional, D’Alfonso, Sandra, additional, Traynor, Bryan J., additional, Van Damme, Philip, additional, Robberecht, Wim, additional, Brown, Robert H., additional, Landers, John E., additional, Hardiman, Orla, additional, Lewis, Cathryn M., additional, van den Berg, Leonard H., additional, Shaw, Christopher E., additional, Veldink, Jan H., additional, Silani, Vincenzo, additional, Al-Chalabi, Ammar, additional, and Powell, John, additional
Published: 2016
Full Text: View/download PDF

213. Large-scale screening in sporadic amyotrophic lateral sclerosis identifies genetic modifiers in C9orf72 repeat carriers

Author: Dekker, Annelot M., primary, Seelen, Meinie, additional, van Doormaal, Perry T.C., additional, van Rheenen, Wouter, additional, Bothof, Reinoud J.P., additional, van Riessen, Tim, additional, Brands, William J., additional, van der Kooi, Anneke J., additional, de Visser, Marianne, additional, Voermans, Nicol C., additional, Pasterkamp, R. Jeroen, additional, Veldink, Jan H., additional, van den Berg, Leonard H., additional, and van Es, Michael A., additional
Published: 2016
Full Text: View/download PDF

214. Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients.

Author: Bennett, Craig L., Dastidar, Somasish G., Ling, Shuo-Chien, Malik, Bilal, Ashe, Travis, Wadhwa, Mandheer, Miller, Derek B., Lee, Changwoo, Mitchell, Matthew B., Van Es, Michael A., Grunseich, Christopher, Chen, Yingzhang, Sopher, Bryce L., Greensmith, Linda, Cleveland, Don W., and La Spada, Albert R.
Subjects: MOTOR neuron diseases, AMYOTROPHIC lateral sclerosis
Abstract: Amyotrophic lateral sclerosis type 4 (ALS4) is a rare, early-onset, autosomal dominant form of ALS, characterized by slow disease progression and sparing of respiratory musculature. Dominant, gain-of-function mutations in the senataxin gene (SETX) cause ALS4, but the mechanistic basis for motor neuron toxicity is unknown. SETX is a RNA-binding protein with a highly conserved helicase domain, but does not possess a low-complexity domain, making it unique among ALS-linked disease proteins. We derived ALS4 mouse models by expressing two different senataxin gene mutations (R2136H and L389S) via transgenesis and knock-in gene targeting. Both approaches yielded SETX mutant mice that develop neuromuscular phenotypes and motor neuron degeneration. Neuropathological characterization of SETX mice revealed nuclear clearing of TDP-43, accompanied by TDP-43 cytosolic mislocalization, consistent with the hallmark pathology observed in human ALS patients. Postmortem material from ALS4 patients exhibited TDP-43 mislocalization in spinal cord motor neurons, and motor neurons from SETX ALS4 mice displayed enhanced stress granule formation. Immunostaining analysis for nucleocytoplasmic transport proteins Ran and RanGAP1 uncovered nuclear membrane abnormalities in the motor neurons of SETX ALS4 mice, and nuclear import was delayed in SETX ALS4 cortical neurons, indicative of impaired nucleocytoplasmic trafficking. SETX ALS4 mice thus recapitulated ALS disease phenotypes in association with TDP-43 mislocalization and provided insight into the basis for TDP-43 histopathology, linking SETX dysfunction to common pathways of ALS motor neuron degeneration. [ABSTRACT FROM AUTHOR]
Published: 2018
Full Text: View/download PDF

215. Brain morphologic changes in asymptomaticC9orf72repeat expansion carriers

Author: Walhout, Renée, primary, Schmidt, Ruben, additional, Westeneng, Henk-Jan, additional, Verstraete, Esther, additional, Seelen, Meinie, additional, van Rheenen, Wouter, additional, de Reus, Marcel A., additional, van Es, Michael A., additional, Hendrikse, Jeroen, additional, Veldink, Jan H., additional, van den Heuvel, Martijn P., additional, and van den Berg, Leonard H., additional
Published: 2015
Full Text: View/download PDF

216. Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis : a multicenter survival study

Author: Van Doormaal, Perry T. C., Ticozzi, Nicola, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Chio, Adriano, Calvo, Andrea, Mora, Gabriele, Restagno, Gabriella, Traynor, Bryan J., Birve, Anna, Lemmens, Robin, Van Es, Michael A., Saris, Christiaan G. J., Blauw, Hylke M., Van Vught, Paul W. J., Groen, Ewout J. N., Corrado, Lucia, Mazzini, Letizia, Del Bo, Roberto, Corti, Stefania, Waibel, Stefan, Meyer, Thomas, Ludolph, Albert C., Goris, An, Van Damme, Philip, Robberecht, Wim, Shatunov, Aleksey, Fogh, Isabella, Andersen, Peter M., D'Alfonso, Sandra, Hardiman, Orla, Cronin, Simon, Rujescu, Dan, Al-Chalabi, Ammar, Landers, John E., Silani, Vincenzo, Van den Berg, Leonard H., Veldink, Jan H., Van Doormaal, Perry T. C., Ticozzi, Nicola, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Chio, Adriano, Calvo, Andrea, Mora, Gabriele, Restagno, Gabriella, Traynor, Bryan J., Birve, Anna, Lemmens, Robin, Van Es, Michael A., Saris, Christiaan G. J., Blauw, Hylke M., Van Vught, Paul W. J., Groen, Ewout J. N., Corrado, Lucia, Mazzini, Letizia, Del Bo, Roberto, Corti, Stefania, Waibel, Stefan, Meyer, Thomas, Ludolph, Albert C., Goris, An, Van Damme, Philip, Robberecht, Wim, Shatunov, Aleksey, Fogh, Isabella, Andersen, Peter M., D'Alfonso, Sandra, Hardiman, Orla, Cronin, Simon, Rujescu, Dan, Al-Chalabi, Ammar, Landers, John E., Silani, Vincenzo, Van den Berg, Leonard H., and Veldink, Jan H.
Published: 2014
Full Text: View/download PDF

217. Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study

Author: van Doormaal, Perry T.C., primary, Ticozzi, Nicola, additional, Gellera, Cinzia, additional, Ratti, Antonia, additional, Taroni, Franco, additional, Chiò, Adriano, additional, Calvo, Andrea, additional, Mora, Gabriele, additional, Restagno, Gabriella, additional, Traynor, Bryan J., additional, Birve, Anna, additional, Lemmens, Robin, additional, van Es, Michael A., additional, Saris, Christiaan G.J., additional, Blauw, Hylke M., additional, van Vught, Paul W.J., additional, Groen, Ewout J.N., additional, Corrado, Lucia, additional, Mazzini, Letizia, additional, Del Bo, Roberto, additional, Corti, Stefania, additional, Waibel, Stefan, additional, Meyer, Thomas, additional, Ludolph, Albert C., additional, Goris, An, additional, van Damme, Philip, additional, Robberecht, Wim, additional, Shatunov, Aleksey, additional, Fogh, Isabella, additional, Andersen, Peter M., additional, D'Alfonso, Sandra, additional, Hardiman, Orla, additional, Cronin, Simon, additional, Rujescu, Dan, additional, Al-Chalabi, Ammar, additional, Landers, John E., additional, Silani, Vincenzo, additional, van den Berg, Leonard H., additional, and Veldink, Jan H., additional
Published: 2014
Full Text: View/download PDF

218. Depolarized Inactivation Overcomes Impaired Activation to Produce DRG Neuron Hyperexcitability in a Nav1.7 Mutation in a Patient with Distal Limb Pain

Author: Huang, Jianying, primary, Yang, Yang, additional, Dib-Hajj, Sulayman D., additional, van Es, Michael, additional, Zhao, Peng, additional, Salomon, Jody, additional, Drenth, Joost P.H., additional, and Waxman, Stephen G., additional
Published: 2014
Full Text: View/download PDF

219. No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy

Author: Seelen, Meinie, primary, Visser, Anne E., additional, Overste, Daniel J., additional, Kim, Hong J., additional, Palud, A., additional, Wong, Tsz H., additional, van Swieten, John C., additional, Scheltens, Philip, additional, Voermans, Nicol C., additional, Baas, Frank, additional, de Jong, J.M.B.V., additional, van der Kooi, Anneke J., additional, de Visser, Marianne, additional, Veldink, Jan H., additional, Taylor, J. Paul, additional, Van Es, Michael A., additional, and van den Berg, Leonard H., additional
Published: 2014
Full Text: View/download PDF

220. C9orf72andUNC13Aare shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: A genome-wide meta-analysis

Author: Diekstra, Frank P., primary, Van Deerlin, Vivianna M., additional, van Swieten, John C., additional, Al-Chalabi, Ammar, additional, Ludolph, Albert C., additional, Weishaupt, Jochen H., additional, Hardiman, Orla, additional, Landers, John E., additional, Brown, Robert H., additional, van Es, Michael A., additional, Pasterkamp, R. Jeroen, additional, Koppers, Max, additional, Andersen, Peter M., additional, Estrada, Karol, additional, Rivadeneira, Fernando, additional, Hofman, Albert, additional, Uitterlinden, André G., additional, van Damme, Philip, additional, Melki, Judith, additional, Meininger, Vincent, additional, Shatunov, Aleksey, additional, Shaw, Christopher E., additional, Leigh, P. Nigel, additional, Shaw, Pamela J., additional, Morrison, Karen E., additional, Fogh, Isabella, additional, Chiò, Adriano, additional, Traynor, Bryan J., additional, Czell, David, additional, Weber, Markus, additional, Heutink, Peter, additional, de Bakker, Paul I. W., additional, Silani, Vincenzo, additional, Robberecht, Wim, additional, van den Berg, Leonard H., additional, and Veldink, Jan H., additional
Published: 2014
Full Text: View/download PDF

221. Serum angiogenin levels are elevated in ALS, but not Parkinson's disease: Table 1

Author: van Es, Michael A, primary, Veldink, Jan H, additional, Schelhaas, Helenius J, additional, Bloem, Bastiaan R, additional, Sodaar, Peter, additional, van Nuenen, Bart F L, additional, Verbeek, Marcel, additional, van de Warrenburg, Bart P, additional, and van den Berg, Leonard H, additional
Published: 2014
Full Text: View/download PDF

222. H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis

Author: van Rheenen, Wouter, Diekstra, Frank P, van Doormaal, Perry TC, Seelen, Meinie, Kenna, Kevin, McLaughlin, Russell, Shatunov, Aleksey, Czell, David, van Es, Michael A, van Vught, Paul WJ, van Damme, Philip, Smith, Bradley N, Waibel, Stefan, Schelhaas, H Jurgen, van der Kooi, Anneke J, de Visser, Marianne, Weber, Markus, Robberecht, Wim, Hardiman, Orla, Shawi, Pamela J, Shaw, Christopher E, Morrison, Karen E, Al-Chalabi, Ammar, Andersen, Peter M, Ludolph, Albert C, Veldink, Jan H, van den Berg, Leonard H, van Rheenen, Wouter, Diekstra, Frank P, van Doormaal, Perry TC, Seelen, Meinie, Kenna, Kevin, McLaughlin, Russell, Shatunov, Aleksey, Czell, David, van Es, Michael A, van Vught, Paul WJ, van Damme, Philip, Smith, Bradley N, Waibel, Stefan, Schelhaas, H Jurgen, van der Kooi, Anneke J, de Visser, Marianne, Weber, Markus, Robberecht, Wim, Hardiman, Orla, Shawi, Pamela J, Shaw, Christopher E, Morrison, Karen E, Al-Chalabi, Ammar, Andersen, Peter M, Ludolph, Albert C, Veldink, Jan H, and van den Berg, Leonard H
Abstract: The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival. (C) 2013 Elsevier Inc. All rights reserved.
Published: 2013
Full Text: View/download PDF

223. Sober houses : the role of the environment in aiding recovering from addiction : a thesis presented in partial fulfilment of the requirements for the degree of Master of Arts in Psychology at Massey University, Wellington, New Zealand

Author: Van Es, Michael James and Van Es, Michael James
Abstract: There is a need for a deeper understanding of the role that the environment plays in an individual’s addiction to substances and in aiding recovery from addiction. The aim of the present study is to investigate the impacts the environment has on individual attempts at recovering from substance addiction, by learning from residents of sober-houses. Sober-houses are substance-free living environments for persons attempting to abstain from alcohol or drugs. Qualitative methodologies were employed, with an Interpretative Phenomenological Analysis (IPA) approach, to take into account the subjective individual differences between residents. A sample of five participants was drawn from residents of a sober-house to participate in semi-structured interviews. The results showed that the most significant impacts on addiction recovery occur with the domain of the social and physical environments. Participants were shown to be able to benefit from physically distancing themselves from destructive environments, and that positive social influences play important roles in the promotion of a sober life-style.
Published: 2013

224. Mapping of Gene Expression Reveals CYP27A1 as a Susceptibility Gene for Sporadic ALS

Author: Diekstra, Frank P., Saris, Christiaan G. J., van Rheenen, Wouter, Franke, Lude, Jansen, Ritsert C., van Es, Michael A., van Vught, Paul W. J., Blauw, Hylke M., Groen, Ewout J. N., Horvath, Steve, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G., Robberecht, Wim, Andersen, Peter M., Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E., Brown, Robert H., Jr., Shatunov, Aleksey, Shaw, Christopher E., Leigh, P. Nigel, Al-Chalabi, Ammar, Ophoff, Roel A., van den Berg, Leonard H., Veldink, Jan H., Diekstra, Frank P., Saris, Christiaan G. J., van Rheenen, Wouter, Franke, Lude, Jansen, Ritsert C., van Es, Michael A., van Vught, Paul W. J., Blauw, Hylke M., Groen, Ewout J. N., Horvath, Steve, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G., Robberecht, Wim, Andersen, Peter M., Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E., Brown, Robert H., Jr., Shatunov, Aleksey, Shaw, Christopher E., Leigh, P. Nigel, Al-Chalabi, Ammar, Ophoff, Roel A., van den Berg, Leonard H., and Veldink, Jan H.
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 x 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for ALS
Published: 2012
Full Text: View/download PDF

225. Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis

Author: Bogaert, Elke, Goris, An, Van Damme, Philip, Geelen, Veerle, Lemmens, Robin, van Es, Michael A, van den Berg, Leonard H, Sleegers, Kristel, Verpoorten, Nathalie, Timmerman, Vincent, Jonghe, Peter De, Van Broeckhoven, Christine, Traynor, Bryan J, Landers, John E, Brown, Robert H, Glass, Jonathan D, Al-Chalabi, Ammar, Shaw, Christopher E, Birve, Anna, Andersen, Peter M, Slowik, Agnieszka, Tomik, Barbara, Melki, Judith, Robberecht, Wim, Van Den Bosch, Ludo, Bogaert, Elke, Goris, An, Van Damme, Philip, Geelen, Veerle, Lemmens, Robin, van Es, Michael A, van den Berg, Leonard H, Sleegers, Kristel, Verpoorten, Nathalie, Timmerman, Vincent, Jonghe, Peter De, Van Broeckhoven, Christine, Traynor, Bryan J, Landers, John E, Brown, Robert H, Glass, Jonathan D, Al-Chalabi, Ammar, Shaw, Christopher E, Birve, Anna, Andersen, Peter M, Slowik, Agnieszka, Tomik, Barbara, Melki, Judith, Robberecht, Wim, and Van Den Bosch, Ludo
Abstract: Excitotoxicity is thought to play a pathogenic role in amyotrophic lateral sclerosis (ALS). Excitotoxic motor neuron death is mediated through the Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type of glutamate receptors and Ca(2+) permeability is determined by the GluR2 subunit. We investigated whether polymorphisms or mutations in the GluR2 gene (GRIA2) predispose patients to ALS. Upon sequencing 24 patients and 24 controls no nonsynonymous coding variants were observed but 24 polymorphisms were identified, 9 of which were novel. In a screening set of 310 Belgian ALS cases and 794 healthy controls and a replication set of 3157 cases and 5397 controls from 6 additional populations no association with susceptibility, age at onset, or disease duration was observed. We conclude that polymorphisms in the GluR2 gene (GRIA2) are not a major contributory factor in the pathogenesis of ALS.
Published: 2012
Full Text: View/download PDF

226. Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.

Author: Diekstra, Frank P, Diekstra, Frank P, Saris, Christiaan GJ, van Rheenen, Wouter, Franke, Lude, Jansen, Ritsert C, van Es, Michael A, van Vught, Paul WJ, Blauw, Hylke M, Groen, Ewout JN, Horvath, Steve, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G, Robberecht, Wim, Andersen, Peter M, Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E, Brown, Robert H, Shatunov, Aleksey, Shaw, Christopher E, Leigh, P Nigel, Al-Chalabi, Ammar, Ophoff, Roel A, van den Berg, Leonard H, Veldink, Jan H, Diekstra, Frank P, Diekstra, Frank P, Saris, Christiaan GJ, van Rheenen, Wouter, Franke, Lude, Jansen, Ritsert C, van Es, Michael A, van Vught, Paul WJ, Blauw, Hylke M, Groen, Ewout JN, Horvath, Steve, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G, Robberecht, Wim, Andersen, Peter M, Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E, Brown, Robert H, Shatunov, Aleksey, Shaw, Christopher E, Leigh, P Nigel, Al-Chalabi, Ammar, Ophoff, Roel A, van den Berg, Leonard H, and Veldink, Jan H
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 × 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for ALS
Published: 2012

227. Mapping of Gene Expression Reveals CYP27A1 as a Susceptibility Gene for Sporadic ALS

Author: Brug, Marcel P. van der, Diekstra, Frank P., Saris, Christiaan G. J., van Rheenen, Wouter, Franke, Lude, Jansen, Ritsert C., van Es, Michael A., van Vught, Paul W. J., Blauw, Hylke M., Groen, Ewout J. N., Horvath, Steve, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G., Robberecht, Wim, Andersen, Peter M., Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E., Brown, Robert H., Shatunov, Aleksey, Shaw, Christopher E., Leigh, P. Nigel, Al-Chalabi, Ammar, Ophoff, Roel A., van den Berg, Leonard H., Veldink, Jan H., Brown Jr., Robert H., Brug, Marcel P. van der, Diekstra, Frank P., Saris, Christiaan G. J., van Rheenen, Wouter, Franke, Lude, Jansen, Ritsert C., van Es, Michael A., van Vught, Paul W. J., Blauw, Hylke M., Groen, Ewout J. N., Horvath, Steve, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G., Robberecht, Wim, Andersen, Peter M., Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E., Brown, Robert H., Shatunov, Aleksey, Shaw, Christopher E., Leigh, P. Nigel, Al-Chalabi, Ammar, Ophoff, Roel A., van den Berg, Leonard H., Veldink, Jan H., and Brown Jr., Robert H.
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 x 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for
Published: 2012

228. Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Author: van Es, Michael A, Schelhaas, Helenius J, van Vught, Paul W J, Ticozzi, Nicola, Andersen, Peter M, Groen, Ewout J N, Schulte, Claudia, Blauw, Hylke M, Koppers, Max, Diekstra, Frank P, Fumoto, Katsumi, LeClerc, Ashley Lyn, Keagle, Pamela, Bloem, Bastiaan R, Scheffer, Hans, van Nuenen, Bart F L, van Blitterswijk, Marka, van Rheenen, Wouter, Wills, Anne-Marie, Lowe, Patrick P, Hu, Guo-fu, Yu, Wenhao, Kishikawa, Hiroko, Wu, David, Folkerth, Rebecca D, Mariani, Claudio, Goldwurm, Stefano, Pezzoli, Gianni, Van Damme, Philip, Lemmens, Robin, Dahlberg, Caroline, Birve, Anna, Fernández-Santiago, Rubén, Waibel, Stefan, Klein, Christine, Weber, Markus, van der Kooi, Anneke J, de Visser, Marianne, Verbaan, Dagmar, van Hilten, Jacobus J, Heutink, Peter, Hennekam, Eric A M, Cuppen, Edwin, Berg, Daniela, Brown, Robert H, Silani, Vincenzo, Gasser, Thomas, Ludolph, Albert C, Robberecht, Wim, Ophoff, Roel A, Veldink, Jan H, Pasterkamp, R Jeroen, de Bakker, Paul I W, Landers, John E, van de Warrenburg, Bart P, van den Berg, Leonard H, van Es, Michael A, Schelhaas, Helenius J, van Vught, Paul W J, Ticozzi, Nicola, Andersen, Peter M, Groen, Ewout J N, Schulte, Claudia, Blauw, Hylke M, Koppers, Max, Diekstra, Frank P, Fumoto, Katsumi, LeClerc, Ashley Lyn, Keagle, Pamela, Bloem, Bastiaan R, Scheffer, Hans, van Nuenen, Bart F L, van Blitterswijk, Marka, van Rheenen, Wouter, Wills, Anne-Marie, Lowe, Patrick P, Hu, Guo-fu, Yu, Wenhao, Kishikawa, Hiroko, Wu, David, Folkerth, Rebecca D, Mariani, Claudio, Goldwurm, Stefano, Pezzoli, Gianni, Van Damme, Philip, Lemmens, Robin, Dahlberg, Caroline, Birve, Anna, Fernández-Santiago, Rubén, Waibel, Stefan, Klein, Christine, Weber, Markus, van der Kooi, Anneke J, de Visser, Marianne, Verbaan, Dagmar, van Hilten, Jacobus J, Heutink, Peter, Hennekam, Eric A M, Cuppen, Edwin, Berg, Daniela, Brown, Robert H, Silani, Vincenzo, Gasser, Thomas, Ludolph, Albert C, Robberecht, Wim, Ophoff, Roel A, Veldink, Jan H, Pasterkamp, R Jeroen, de Bakker, Paul I W, Landers, John E, van de Warrenburg, Bart P, and van den Berg, Leonard H
Abstract: OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
Published: 2011
Full Text: View/download PDF

229. Large-scale SOD1 mutation screening provides evidence for genetic heterogeneity in amyotrophic lateral sclerosis.

Author: van Es, Michael A, Dahlberg, Caroline, Birve, Anna, Veldink, Jan Herman, van den Berg, Leonard H, Andersen, Peter M, van Es, Michael A, Dahlberg, Caroline, Birve, Anna, Veldink, Jan Herman, van den Berg, Leonard H, and Andersen, Peter M
Abstract: OBJECTIVE: To estimate the frequency of SOD1 mutations in a large referral cohort of familial amyotrophic lateral sclerosis (FALS) and sporadic amyotrophic lateral sclerosis (SALS) patients from The Netherlands and to compare this frequency with that of other developed countries. METHODS: A total of 451 sporadic and 55 FALS patients were screened for SOD1 mutations. The authors performed PCR amplification of all five coding exons of SOD1 followed by direct DNA sequencing using forward and reverse primers. RESULTS: One novel mutation (p.I99V) and a homozygous p.D90A mutation were identified in SALS patients. In a pedigree with Mendelian dominant FALS, one patient was found to be heterozygous for the p.D90A mutation. SOD1 mutation frequency was found to be significantly lower in The Netherlands compared with other countries with p=0.0004 for FALS (21.9% vs 2.5%) and p=0.005 for SALS (2.5% vs 0.44%). CONCLUSIONS: The authors demonstrate that SOD1 mutations are rare in The Netherlands in familial and SALS. This observation suggests that the genetic background of amyotrophic lateral sclerosis differs between different populations, countries and regions. This may have consequences for the interpretation of association studies and explain why replication of association studies has proven difficult in amyotrophic lateral sclerosis.
Published: 2010
Full Text: View/download PDF

230. A large genome scan for rare CNVs in amyotrophic lateral sclerosis

Author: Blauw, Hylke M, Al-Chalabi, Ammar, Andersen, Peter M, van Vught, Paul W J, Diekstra, Frank P, van Es, Michael A, Saris, Christiaan G J, Groen, Ewout J N, van Rheenen, Wouter, Koppers, Max, Van't Slot, Ruben, Strengman, Eric, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G, Kiemeney, Lambertus A, Vermeulen, Sita H M, Birve, Anna, Waibel, Stefan, Meyer, Thomas, Cronin, Simon, McLaughlin, Russell L, Hardiman, Orla, Sapp, Peter C, Tobin, Martin D, Wain, Louise V, Tomik, Barbara, Slowik, Agnieszka, Lemmens, Robin, Rujescu, Dan, Schulte, Claudia, Gasser, Thomas, Brown, Robert H, Landers, John E, Robberecht, Wim, Ludolph, Albert C, Ophoff, Roel A, Veldink, Jan H, van den Berg, Leonard H, Blauw, Hylke M, Al-Chalabi, Ammar, Andersen, Peter M, van Vught, Paul W J, Diekstra, Frank P, van Es, Michael A, Saris, Christiaan G J, Groen, Ewout J N, van Rheenen, Wouter, Koppers, Max, Van't Slot, Ruben, Strengman, Eric, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G, Kiemeney, Lambertus A, Vermeulen, Sita H M, Birve, Anna, Waibel, Stefan, Meyer, Thomas, Cronin, Simon, McLaughlin, Russell L, Hardiman, Orla, Sapp, Peter C, Tobin, Martin D, Wain, Louise V, Tomik, Barbara, Slowik, Agnieszka, Lemmens, Robin, Rujescu, Dan, Schulte, Claudia, Gasser, Thomas, Brown, Robert H, Landers, John E, Robberecht, Wim, Ludolph, Albert C, Ophoff, Roel A, Veldink, Jan H, and van den Berg, Leonard H
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase disease susceptibility. In contrast, rare copy-number variants (CNVs), which have been associated with several neuropsychiatric traits, have not been studied for ALS in well-powered study populations. To examine the role of rare CNVs in ALS susceptibility, we conducted a CNV association study including over 19,000 individuals. In a genome-wide screen of 1875 cases and 8731 controls, we did not find evidence for a difference in global CNV burden between cases and controls. In our association analyses, we identified two loci that met our criteria for follow-up: the DPP6 locus (OR = 3.59, P = 6.6 × 10(-3)), which has already been implicated in ALS pathogenesis, and the 15q11.2 locus, containing NIPA1 (OR = 12.46, P = 9.3 × 10(-5)), the gene causing hereditary spastic paraparesis type 6 (HSP 6). We tested these loci in a replication cohort of 2559 cases and 5887 controls. Again, results were suggestive of association, but did not meet our criteria for independent replication: DPP6 locus: OR = 1.92, P = 0.097, pooled results: OR = 2.64, P = 1.4 × 10(-3); NIPA1: OR = 3.23, P = 0.041, pooled results: OR = 6.20, P = 2.2 × 10(-5)). Our results highlight DPP6 and NIPA1 as candidates for more in-depth studies. Unlike other complex neurological and psychiatric traits, rare CNVs with high effect size do not play a major role in ALS pathogenesis.
Published: 2010
Full Text: View/download PDF

231. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries : a genome-wide association study

Author: Shatunov, Aleksey, Mok, Kin, Newhouse, Stephen, Weale, Michael E, Smith, Bradley, Vance, Caroline, Johnson, Lauren, Veldink, Jan H, van Es, Michael A, van den Berg, Leonard H, Robberecht, Wim, Van Damme, Philip, Hardiman, Orla, Farmer, Anne E, Lewis, Cathryn M, Butler, Amy W, Abel, Olubunmi, Andersen, Peter M, Fogh, Isabella, Silani, Vincenzo, Chiò, Adriano, Traynor, Bryan J, Melki, Judith, Meininger, Vincent, Landers, John E, McGuffin, Peter, Glass, Jonathan D, Pall, Hardev, Leigh, P Nigel, Hardy, John, Brown, Robert H, Powell, John F, Orrell, Richard W, Morrison, Karen E, Shaw, Pamela J, Shaw, Christopher E, Al-Chalabi, Ammar, Shatunov, Aleksey, Mok, Kin, Newhouse, Stephen, Weale, Michael E, Smith, Bradley, Vance, Caroline, Johnson, Lauren, Veldink, Jan H, van Es, Michael A, van den Berg, Leonard H, Robberecht, Wim, Van Damme, Philip, Hardiman, Orla, Farmer, Anne E, Lewis, Cathryn M, Butler, Amy W, Abel, Olubunmi, Andersen, Peter M, Fogh, Isabella, Silani, Vincenzo, Chiò, Adriano, Traynor, Bryan J, Melki, Judith, Meininger, Vincent, Landers, John E, McGuffin, Peter, Glass, Jonathan D, Pall, Hardev, Leigh, P Nigel, Hardy, John, Brown, Robert H, Powell, John F, Orrell, Richard W, Morrison, Karen E, Shaw, Pamela J, Shaw, Christopher E, and Al-Chalabi, Ammar
Abstract: We have found strong evidence of a genetic association of two single nucleotide polymorphisms on chromosome 9 with sporadic ALS, in line with findings from previous independent GWAS of ALS and linkage studies of ALS-frontotemporal dementia. Our findings together with these earlier findings suggest that genetic variation at this locus on chromosome 9 causes sporadic ALS and familial ALS-frontotemporal dementia. Resequencing studies and then functional analysis should be done to identify the defective gene.
Published: 2010
Full Text: View/download PDF

232. Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis

Author: Van Es, Michael A, Van Vught, Paul W J, Veldink, Jan H, Andersen, Peter M, Birve, Anna, Lemmens, Robin, Cronin, Simon, Van Der Kooi, Anneke J, De Visser, Marianne, Schelhaas, Helenius J, Hardiman, Orla, Ragoussis, Ioannis, Lambrechts, Diether, Robberecht, Wim, Wokke, John H J, Ophoff, Roel A, Van Den Berg, Leonard H, Van Es, Michael A, Van Vught, Paul W J, Veldink, Jan H, Andersen, Peter M, Birve, Anna, Lemmens, Robin, Cronin, Simon, Van Der Kooi, Anneke J, De Visser, Marianne, Schelhaas, Helenius J, Hardiman, Orla, Ragoussis, Ioannis, Lambrechts, Diether, Robberecht, Wim, Wokke, John H J, Ophoff, Roel A, and Van Den Berg, Leonard H
Abstract: A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS, independent replication of associations is crucial for identifying true-positive genetic risk factors for disease. The primary aim of this study was to study the association between FGGY and sporadic ALS in large, homogeneous populations from northern Europe. Genotyping experiments were performed using Illumina Beadchips, Sequenom iPLEX assays and Taqman technology on large case-control series from The Netherlands, Belgium, Sweden and Ireland (total: 1883 sporadic ALS patients and 2063 controls). No significant association between sporadic ALS and the six previously reported associated SNPs in FGGY was observed: rs6700125 (p =0.56), rs6690993 (p =0.30), rs10493256 (p =0.68), rs6587852 (p =0.64), rs1470407 (p =0.28) and rs333662 (p =0.44). Screening of the additional candidate loci did not yield significant associations either, with the lowest p-value in joint analysis for rs7772593 (p =0.14). We concluded that common genetic variation in FGGY is not associated with susceptibility to sporadic ALS in genetically homogeneous populations from northern Europe.
Published: 2009
Full Text: View/download PDF

233. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis

Author: van Es, Michael A, Veldink, Jan H, Saris, Christiaan G J, Blauw, Hylke M, van Vught, Paul W J, Birve, Anna, Lemmens, Robin, Schelhaas, Helenius J, Groen, Ewout J N, Huisman, Mark H B, van der Kooi, Anneke J, de Visser, Marianne, Dahlberg, Caroline, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Zwarts, Machiel J, van Doormaal, Perry T C, Rujescu, Dan, Strengman, Eric, Giegling, Ina, Muglia, Pierandrea, Tomik, Barbara, Slowik, Agnieszka, Uitterlinden, Andre G, Hendrich, Corinna, Waibel, Stefan, Meyer, Thomas, Ludolph, Albert C, Glass, Jonathan D, Purcell, Shaun, Cichon, Sven, Nöthen, Markus M, Wichmann, H-Erich, Schreiber, Stefan, Vermeulen, Sita H H M, Kiemeney, Lambertus A, Wokke, John H J, Cronin, Simon, McLaughlin, Russell L, Hardiman, Orla, Fumoto, Katsumi, Pasterkamp, R Jeroen, Meininger, Vincent, Melki, Judith, Leigh, P Nigel, Shaw, Christopher E, Landers, John E, Al-Chalabi, Ammar, Brown, Robert H, Robberecht, Wim, Andersen, Peter M, Ophoff, Roel A, van den Berg, Leonard H, van Es, Michael A, Veldink, Jan H, Saris, Christiaan G J, Blauw, Hylke M, van Vught, Paul W J, Birve, Anna, Lemmens, Robin, Schelhaas, Helenius J, Groen, Ewout J N, Huisman, Mark H B, van der Kooi, Anneke J, de Visser, Marianne, Dahlberg, Caroline, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Zwarts, Machiel J, van Doormaal, Perry T C, Rujescu, Dan, Strengman, Eric, Giegling, Ina, Muglia, Pierandrea, Tomik, Barbara, Slowik, Agnieszka, Uitterlinden, Andre G, Hendrich, Corinna, Waibel, Stefan, Meyer, Thomas, Ludolph, Albert C, Glass, Jonathan D, Purcell, Shaun, Cichon, Sven, Nöthen, Markus M, Wichmann, H-Erich, Schreiber, Stefan, Vermeulen, Sita H H M, Kiemeney, Lambertus A, Wokke, John H J, Cronin, Simon, McLaughlin, Russell L, Hardiman, Orla, Fumoto, Katsumi, Pasterkamp, R Jeroen, Meininger, Vincent, Melki, Judith, Leigh, P Nigel, Shaw, Christopher E, Landers, John E, Al-Chalabi, Ammar, Brown, Robert H, Robberecht, Wim, Andersen, Peter M, Ophoff, Roel A, and van den Berg, Leonard H
Abstract: We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
Published: 2009
Full Text: View/download PDF

234. Gene-network analysis identifies susceptibility genes related to glycobiology in autism.

Author: van der Zwaag, Bert, van der Zwaag, Bert, Franke, Lude, Poot, Martin, Hochstenbach, Ron, Spierenburg, Henk A, Vorstman, Jacob AS, van Daalen, Emma, de Jonge, Maretha V, Verbeek, Nienke E, Brilstra, Eva H, van 't Slot, Ruben, Ophoff, Roel A, van Es, Michael A, Blauw, Hylke M, Veldink, Jan H, Buizer-Voskamp, Jacobine E, Beemer, Frits A, van den Berg, Leonard H, Wijmenga, Cisca, van Amstel, Hans Kristian Ploos, van Engeland, Herman, Burbach, J Peter H, Staal, Wouter G, van der Zwaag, Bert, van der Zwaag, Bert, Franke, Lude, Poot, Martin, Hochstenbach, Ron, Spierenburg, Henk A, Vorstman, Jacob AS, van Daalen, Emma, de Jonge, Maretha V, Verbeek, Nienke E, Brilstra, Eva H, van 't Slot, Ruben, Ophoff, Roel A, van Es, Michael A, Blauw, Hylke M, Veldink, Jan H, Buizer-Voskamp, Jacobine E, Beemer, Frits A, van den Berg, Leonard H, Wijmenga, Cisca, van Amstel, Hans Kristian Ploos, van Engeland, Herman, Burbach, J Peter H, and Staal, Wouter G
Abstract: The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.
Published: 2009

235. Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

Author: Saris, Christiaan GJ, Saris, Christiaan GJ, Horvath, Steve, van Vught, Paul WJ, van Es, Michael A, Blauw, Hylke M, Fuller, Tova F, Langfelder, Peter, DeYoung, Joseph, Wokke, John HJ, Veldink, Jan H, van den Berg, Leonard H, Ophoff, Roel A, Saris, Christiaan GJ, Saris, Christiaan GJ, Horvath, Steve, van Vught, Paul WJ, van Es, Michael A, Blauw, Hylke M, Fuller, Tova F, Langfelder, Peter, DeYoung, Joseph, Wokke, John HJ, Veldink, Jan H, van den Berg, Leonard H, and Ophoff, Roel A
Abstract: Background Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients. Results Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS. Conclusion This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.
Published: 2009

236. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis.

Author: van Es, Michael A, van Vught, Paul W J, Blauw, Hylke M, Franke, Lude, Saris, Christiaan G J, Van den Bosch, Ludo, de Jong, Sonja W, de Jong, Vianney, Baas, Frank, van't Slot, Ruben, Lemmens, Robin, Schelhaas, Helenius J, Birve, Anna, Sleegers, Kristel, Van Broeckhoven, Christine, Schymick, Jennifer C, Traynor, Bryan J, Wokke, John H J, Wijmenga, Cisca, Robberecht, Wim, Andersen, Peter M, Veldink, Jan H, Ophoff, Roel A, van den Berg, Leonard H, van Es, Michael A, van Vught, Paul W J, Blauw, Hylke M, Franke, Lude, Saris, Christiaan G J, Van den Bosch, Ludo, de Jong, Sonja W, de Jong, Vianney, Baas, Frank, van't Slot, Ruben, Lemmens, Robin, Schelhaas, Helenius J, Birve, Anna, Sleegers, Kristel, Van Broeckhoven, Christine, Schymick, Jennifer C, Traynor, Bryan J, Wokke, John H J, Wijmenga, Cisca, Robberecht, Wim, Andersen, Peter M, Veldink, Jan H, Ophoff, Roel A, and van den Berg, Leonard H
Abstract: We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04 x 10(-8) in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18-1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies.
Published: 2008
Full Text: View/download PDF

237. Screening for rare variants in the coding region of ALS-associated genes at 9p21.2 and 19p13.3

Author: Koppers, Max, primary, Groen, Ewout J.N., additional, van Vught, Paul W.J., additional, van Rheenen, Wouter, additional, Witteveen, Esther, additional, van Es, Michael A., additional, Pasterkamp, R. Jeroen, additional, van den Berg, Leonard H., additional, and Veldink, Jan H., additional
Published: 2013
Full Text: View/download PDF

238. Mutational analysis of TARDBP in Parkinson's disease

Author: van Blitterswijk, Marka, primary, van Es, Michael A., additional, Verbaan, Dagmar, additional, van Hilten, Jacobus J., additional, Scheffer, Hans, additional, van de Warrenburg, Bart P., additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional
Published: 2013
Full Text: View/download PDF

239. H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis

Author: van Rheenen, Wouter, primary, Diekstra, Frank P., additional, van Doormaal, Perry T.C., additional, Seelen, Meinie, additional, Kenna, Kevin, additional, McLaughlin, Russell, additional, Shatunov, Aleksey, additional, Czell, David, additional, van Es, Michael A., additional, van Vught, Paul W.J., additional, van Damme, Philip, additional, Smith, Bradley N., additional, Waibel, Stefan, additional, Schelhaas, H. Jurgen, additional, van der Kooi, Anneke J., additional, de Visser, Marianne, additional, Weber, Markus, additional, Robberecht, Wim, additional, Hardiman, Orla, additional, Shaw, Pamela J., additional, Shaw, Christopher E., additional, Morrison, Karen E., additional, Al-Chalabi, Ammar, additional, Andersen, Peter M., additional, Ludolph, Albert C., additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional
Published: 2013
Full Text: View/download PDF

240. Gene expression profile of SOD1-G93A mouse spinal cord, blood and muscle

Author: Saris, Christiaan G. J., primary, Groen, Ewout J. N., additional, Van Vught, Paul W. J., additional, van Es, Michael A., additional, Blauw, Hylke M., additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional
Published: 2013
Full Text: View/download PDF

241. Brain morphologic changes in asymptomatic C9orf72 repeat expansion carriers.

Author: Walhout, Renée, Schmidt, Ruben, Westeneng, Henk-Jan, Verstraete, Esther, Seelen, Meinie, van Rheenen, Wouter, de Reus, Marcel A., van Es, Michael A., Hendrikse, Jeroen, Veldink, Jan H., van den Heuvel, Martijn P., and van den Berg, Leonard H.
Published: 2015
Full Text: View/download PDF

242. VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient

Author: van Blitterswijk, Marka, primary, van Es, Michael A., additional, Koppers, Max, additional, van Rheenen, Wouter, additional, Medic, Jelena, additional, Schelhaas, Helenius J., additional, van der Kooi, Anneke J., additional, de Visser, Marianne, additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional
Published: 2012
Full Text: View/download PDF

243. Genetic Overlap between Apparently Sporadic Motor Neuron Diseases

Author: van Blitterswijk, Marka, primary, Vlam, Lotte, additional, van Es, Michael A., additional, van der Pol, W-Ludo, additional, Hennekam, Eric A. M., additional, Dooijes, Dennis, additional, Schelhaas, Helenius J., additional, van der Kooi, Anneke J., additional, de Visser, Marianne, additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional
Published: 2012
Full Text: View/download PDF

244. Mapping of Gene Expression Reveals CYP27A1 as a Susceptibility Gene for Sporadic ALS

Author: Diekstra, Frank P., primary, Saris, Christiaan G. J., additional, van Rheenen, Wouter, additional, Franke, Lude, additional, Jansen, Ritsert C., additional, van Es, Michael A., additional, van Vught, Paul W. J., additional, Blauw, Hylke M., additional, Groen, Ewout J. N., additional, Horvath, Steve, additional, Estrada, Karol, additional, Rivadeneira, Fernando, additional, Hofman, Albert, additional, Uitterlinden, Andre G., additional, Robberecht, Wim, additional, Andersen, Peter M., additional, Melki, Judith, additional, Meininger, Vincent, additional, Hardiman, Orla, additional, Landers, John E., additional, Brown, Robert H., additional, Shatunov, Aleksey, additional, Shaw, Christopher E., additional, Leigh, P. Nigel, additional, Al-Chalabi, Ammar, additional, Ophoff, Roel A., additional, van den Berg, Leonard H., additional, and Veldink, Jan H., additional
Published: 2012
Full Text: View/download PDF

245. Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis

Author: Bogaert, Elke, primary, Goris, An, additional, Van Damme, Philip, additional, Geelen, Veerle, additional, Lemmens, Robin, additional, van Es, Michael A., additional, van den Berg, Leonard H., additional, Sleegers, Kristel, additional, Verpoorten, Nathalie, additional, Timmerman, Vincent, additional, De Jonghe, Peter, additional, Van Broeckhoven, Christine, additional, Traynor, Bryan J., additional, Landers, John E., additional, Brown, Robert H., additional, Glass, Jonathan D., additional, Al-Chalabi, Ammar, additional, Shaw, Christopher E., additional, Birve, Anna, additional, Andersen, Peter M., additional, Slowik, Agnieszka, additional, Tomik, Barbara, additional, Melki, Judith, additional, Robberecht, Wim, additional, and Van Den Bosch, Ludo, additional
Published: 2012
Full Text: View/download PDF

246. Detection of long repeat expansions from PCR-free whole-genome sequence data

Author: Dolzhenko, Egor, van Vugt, Joke J.F.A., Shaw, Richard J., Bekritsky, Mitchell A., van Blitterswijk, Marka, Narzisi, Giuseppe, Ajay, Subramanian S., Rajan, Vani, Lajoie, Bryan R., Johnson, Nathan H., Kingsbury, Zoya, Humphray, Sean J., Schellevis, Raymond D., Brands, William J., Baker, Matt, Rademakers, Rosa, Kooyman, Maarten, Tazelaar, Gijs H.P., van Es, Michael A., McLaughlin, Russell, Sproviero, William, Shatunov, Aleksey, Jones, Ashley, Al Khleifat, Ahmad, Pittman, Alan, Morgan, Sarah, Hardiman, Orla, Al-Chalabi, Ammar, Shaw, Chris, Smith, Bradley, Neo, Edmund J., Morrison, Karen, Shaw, Pamela J., Reeves, Catherine, Winterkorn, Lara, Wexler, Nancy S., Housman, David E., Ng, Christopher W., Li, Alina L., Taft, Ryan J., van den Berg, Leonard H., Bentley, David R., Veldink, Jan H., and Eberle, Michael A.
Abstract: Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3001 ALS patients who have been tested for the presence of the C9orf72repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2786/2789, 95% CI [0.997, 1.00]) of the wild-type samples were correctly classified as wild type by this method with the remaining three samples identified as possible expansions. We further applied our algorithm to a set of 152 samples in which every sample had one of eight different pathogenic repeat expansions, including those associated with fragile X syndrome, Friedreich's ataxia, and Huntington's disease, and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.
Published: 2017
Full Text: View/download PDF

247. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study

Author: Shatunov, Aleksey, primary, Mok, Kin, additional, Newhouse, Stephen, additional, Weale, Michael E, additional, Smith, Bradley, additional, Vance, Caroline, additional, Johnson, Lauren, additional, Veldink, Jan H, additional, van Es, Michael A, additional, van den Berg, Leonard H, additional, Robberecht, Wim, additional, Van Damme, Philip, additional, Hardiman, Orla, additional, Farmer, Anne E, additional, Lewis, Cathryn M, additional, Butler, Amy W, additional, Abel, Olubunmi, additional, Andersen, Peter M, additional, Fogh, Isabella, additional, Silani, Vincenzo, additional, Chiò, Adriano, additional, Traynor, Bryan J, additional, Melki, Judith, additional, Meininger, Vincent, additional, Landers, John E, additional, McGuffin, Peter, additional, Glass, Jonathan D, additional, Pall, Hardev, additional, Leigh, P Nigel, additional, Hardy, John, additional, Brown, Robert H, additional, Powell, John F, additional, Orrell, Richard W, additional, Morrison, Karen E, additional, Shaw, Pamela J, additional, Shaw, Christopher E, additional, and Al-Chalabi, Ammar, additional
Published: 2010
Full Text: View/download PDF

248. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

Author: Kiemeney, Lambertus A, primary, Sulem, Patrick, additional, Besenbacher, Soren, additional, Vermeulen, Sita H, additional, Sigurdsson, Asgeir, additional, Thorleifsson, Gudmar, additional, Gudbjartsson, Daniel F, additional, Stacey, Simon N, additional, Gudmundsson, Julius, additional, Zanon, Carlo, additional, Kostic, Jelena, additional, Masson, Gisli, additional, Bjarnason, Hjordis, additional, Palsson, Stefan T, additional, Skarphedinsson, Oskar B, additional, Gudjonsson, Sigurjon A, additional, Witjes, J Alfred, additional, Grotenhuis, Anne J, additional, Verhaegh, Gerald W, additional, Bishop, D Timothy, additional, Sak, Sei Chung, additional, Choudhury, Ananya, additional, Elliott, Faye, additional, Barrett, Jennifer H, additional, Hurst, Carolyn D, additional, de Verdier, Petra J, additional, Ryk, Charlotta, additional, Rudnai, Peter, additional, Gurzau, Eugene, additional, Koppova, Kvetoslava, additional, Vineis, Paolo, additional, Polidoro, Silvia, additional, Guarrera, Simonetta, additional, Sacerdote, Carlotta, additional, Campagna, Marcello, additional, Placidi, Donatella, additional, Arici, Cecilia, additional, Zeegers, Maurice P, additional, Kellen, Eliane, additional, Gutierrez, Berta Saez, additional, Sanz-Velez, José I, additional, Sanchez-Zalabardo, Manuel, additional, Valdivia, Gabriel, additional, Garcia-Prats, Maria D, additional, Hengstler, Jan G, additional, Blaszkewicz, Meinolf, additional, Dietrich, Holger, additional, Ophoff, Roel A, additional, van den Berg, Leonard H, additional, Alexiusdottir, Kristin, additional, Kristjansson, Kristleifur, additional, Geirsson, Gudmundur, additional, Nikulasson, Sigfus, additional, Petursdottir, Vigdis, additional, Kong, Augustine, additional, Thorgeirsson, Thorgeir, additional, Mungan, N Aydin, additional, Lindblom, Annika, additional, van Es, Michael A, additional, Porru, Stefano, additional, Buntinx, Frank, additional, Golka, Klaus, additional, Mayordomo, José I, additional, Kumar, Rajiv, additional, Matullo, Giuseppe, additional, Steineck, Gunnar, additional, Kiltie, Anne E, additional, Aben, Katja K H, additional, Jonsson, Eirikur, additional, Thorsteinsdottir, Unnur, additional, Knowles, Margaret A, additional, Rafnar, Thorunn, additional, and Stefansson, Kari, additional
Published: 2010
Full Text: View/download PDF

249. Alzheimer’s disease beyond APOE

Author: van Es, Michael A, primary and van den Berg, Leonard H, additional
Published: 2009
Full Text: View/download PDF

250. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis

Author: van Es, Michael A, primary, Veldink, Jan H, additional, Saris, Christiaan G J, additional, Blauw, Hylke M, additional, van Vught, Paul W J, additional, Birve, Anna, additional, Lemmens, Robin, additional, Schelhaas, Helenius J, additional, Groen, Ewout J N, additional, Huisman, Mark H B, additional, van der Kooi, Anneke J, additional, de Visser, Marianne, additional, Dahlberg, Caroline, additional, Estrada, Karol, additional, Rivadeneira, Fernando, additional, Hofman, Albert, additional, Zwarts, Machiel J, additional, van Doormaal, Perry T C, additional, Rujescu, Dan, additional, Strengman, Eric, additional, Giegling, Ina, additional, Muglia, Pierandrea, additional, Tomik, Barbara, additional, Slowik, Agnieszka, additional, Uitterlinden, Andre G, additional, Hendrich, Corinna, additional, Waibel, Stefan, additional, Meyer, Thomas, additional, Ludolph, Albert C, additional, Glass, Jonathan D, additional, Purcell, Shaun, additional, Cichon, Sven, additional, Nöthen, Markus M, additional, Wichmann, H-Erich, additional, Schreiber, Stefan, additional, Vermeulen, Sita H H M, additional, Kiemeney, Lambertus A, additional, Wokke, John H J, additional, Cronin, Simon, additional, McLaughlin, Russell L, additional, Hardiman, Orla, additional, Fumoto, Katsumi, additional, Pasterkamp, R Jeroen, additional, Meininger, Vincent, additional, Melki, Judith, additional, Leigh, P Nigel, additional, Shaw, Christopher E, additional, Landers, John E, additional, Al-Chalabi, Ammar, additional, Brown, Robert H, additional, Robberecht, Wim, additional, Andersen, Peter M, additional, Ophoff, Roel A, additional, and van den Berg, Leonard H, additional
Published: 2009
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

691 results on '"Van Es, Michael A."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources