Author: "Morris H.R." - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Morris H.R."' showing total 142 results

Start Over Author "Morris H.R."

142 results on '"Morris H.R."'

1. Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics

Author: Magdalinou, N.K., Noyce, A.J., Pinto, R., Lindstrom, E., Holmén-Larsson, J., Holtta, M., Blennow, K., Morris, H.R., Skillbäck, T., Warner, T.T., Lees, A.J., Pike, I., Ward, M., Zetterberg, H., and Gobom, J.
Published: 2017
Full Text: View/download PDF

2. The plasma von Willebrand factor O‐glycome comprises a surprising variety of structures including ABH antigens and disialosyl motifs

Author: CANIS, K., MCKINNON, T.A.J., NOWAK, A., PANICO, M., MORRIS, H.R., LAFFAN, M., and DELL, A.
Published: 2010
Full Text: View/download PDF

3. Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease

Author: Lubbe, S.J., Escott-Price, V., Brice, A., Gasser, T., Pittman, A.M., Bras, J., Hardy, J., Heutink, P., Wood, N.M., Singleton, A.B., Grosset, D.G., Carroll, C.B., Law, M.H., Demenais, F., Iles, M.M., Bishop, D.T., Newton-Bishop, J., Williams, N.M., and Morris, H.R.
Published: 2016
Full Text: View/download PDF

4. Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

Author: Chen, Z., Zhang, D., Reynolds, R.H., Gustavsson, E.K., García-Ruiz, S., D'Sa, K., Fairbrother-Browne, A., Vandrovcova, J., Noyce, A.J., Kaiyrzhanov, R., Middlehurst, B., Kia, D.A., Tan, M., Morris, H.R., Plun-Favreau, H., Holmans, P., Trabzuni, D., Bras, J., Quinn, J., Mok, K.Y., Kinghorn, K.J., Billingsley, K., Wood, N.W., Lewis, P., Schreglmann, S., Guerreiro, Rita, Lovering, R., R'Bibo, L., Manzoni, C., Rizig, M., Guelfi, S., Escott-Price, V., Chelban, V., Foltynie, T., Williams, N., Brice, A., Danjou, F., Lesage, S., Corvol, Jean-Christophe, Martinez, M., Schulte, C., Brockmann, K., Simón-Sánchez, J., Heutink, P., Rizzu, P., Sharma, M., Gasser, T., Nicolas, A., Cookson, M. R, Bandres-Ciga, S., Blauwendraat, Cornelis, Craig, David W, Faghri, F., Gibbs, J.R., Hernandez, D.G., Van Keuren-Jensen, K., Shulman, J.M., Leonard, H.L., Nalls, M.A., Robak, L., Lubbe, S., Finkbeiner, S., Mencacci, N.E., Lungu, C., Singleton, A. B., Scholz, S.W., Reed, X., Alcalay, Roy N, Gan-Or, Z., Rouleau, G.A., Krohn, L., van Hilten, J.J., Marinus, J., Adarmes-Gómez, A.D, Aguilar Barberà, Miquel, Alvarez, Ignacio, Alvarez, V., Barrero, F. J, Yarza, J.A.B., Bernal-Bernal, I., Blazquez, M., Bonilla-Toribio, Marta, Botía, J., Boungiorno, M.T., Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, F., Carrión-Claro, M., Cerdan, D., Clarimón, Jordi, Compta, Yaroslau, Diez-Fairen, M., Dols Icardo, Oriol, Duarte, J., Duran, Raquel, Escamilla-Sevilla, F., Ezquerra, M., Feliz, C., Fernández, M., Fernández-Santiago, R., Garcia, C., García-Ruiz, P., Gómez-Garre, P., Heredia, M.J.G., Gonzalez-Aramburu, I., Pagola, A.G., Hoenicka, J., Infante, J., Jesús, S., Jimenez-Escrig, A., Kulisevsky, Jaime, Labrador-Espinosa, Miguel A, Lopez-Sendon, J.L., de Munain Arregui, A.L., Macias, D., Torres, I.M., Marín, J., Marti, M.J., Martínez-Castrillo, J.C., Méndez-del-Barrio, C., González, M.M., Mata, M., Mínguez, A., Mir, P., Rezola, E.M., Muñoz, E., Pagonabarraga Mora, Javier, Pastor, P., Errazquin, F.P., Periñán-Tocino, T., Ruiz-Martínez, J., Ruz, C., Rodriguez, A.S., Sierra, M., Suarez-Sanmartin, E., Tabernero, C., Tartari, J. P., Tejera-Parrado, C., Tolosa, E., Valldeoriola, F., Vargas-González, L., Vela, L., Vives, F., Zimprich, Alexander, Pihlstrom, L., Toft, M., Koks, S., Taba, P., Hassin-Baer, S., Hardy, J., Houlden, Henry, Gagliano Taliun, S. A., Ryten, M., Universitat Autònoma de Barcelona, Universidad de Cantabria, Lord Leonard and Lady Estelle Wolfson Foundation, Medical Research Council (UK), Dementia Research Institute (UK), Alzheimer Society, Alzheimer's Research UK, Wellcome Trust, Dolby Family Fund, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), Agencia Estatal de Investigación (España), Fundación Séneca, and Gobierno de la Región de Murcia
Subjects: 0301 basic medicine, Apolipoprotein E, Aging, Messenger, General Physics and Astronomy, Neurodegenerative, Alzheimer's Disease, Genome, Linkage Disequilibrium, Negative selection, 0302 clinical medicine, 2.1 Biological and endogenous factors, Aetiology, health care economics and organizations, Conserved Sequence, Phylogeny, Multidisciplinary, Brain, Neurodegenerative Diseases, Single Nucleotide, Alzheimer's disease, Phenotype, International Parkinson’s Disease Genomics Consortium, Neurological, Regression Analysis, Long Noncoding, DNA, Intergenic, RNA, Long Noncoding, Human, Biotechnology, Lineage (genetic), Science, 1.1 Normal biological development and functioning, Computational biology, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Chromosomes, 03 medical and health sciences, Apolipoproteins E, Underpinning research, Alzheimer Disease, Genetic variation, Genetics, Acquired Cognitive Impairment, Humans, RNA, Messenger, Polymorphism, Gene, Whole genome sequencing, Intergenic, Pair 19, Genome, Human, Human Genome, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Molecular Sequence Annotation, General Chemistry, DNA, Introns, Brain Disorders, 030104 developmental biology, Gene Ontology, RNA, Dementia, Chromosomes, Human, Pair 19, 030217 neurology & neurosurgery
Abstract: Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer’s disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease., Knowledge of genomic features specific to humans may be important for understanding disease. Here the authors demonstrate a potential role for these human-lineage-specific sequences in brain development and neurological disease.
Published: 2021

5. Finding genetically-supported drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome

Author: Storm, C.S., Kia, D.A., Almramhi, M.M., Bandrés-Ciga, S., Finan, C., Noyce, A.J., Kaiyrzhanov, R., Middlehurst, B., Tan, M., Houlden, H., Morris, H.R., Plun-Favreau, H., Holmans, P., Hardy, J., Trabzuni, D., Quinn, J., Bubb, V., Mok, K.Y., Kinghorn, K.J., Lewis, P., Schreglmann, S.R., Lovering, R., R’Bibo, L., Manzoni, C., Rizig, M., Ryten, M., Guelfi, S., Escott-Price, V., Chelban, V., Foltynie, T., Williams, N., Morrison, K.E., Clarke, C., Harvey, K., Jacobs, B.M., Brice, A., Danjou, F., Lesage, S., Corvol, J-C, Martinez, M., Schulte, C., Brockmann, K., Simón-Sánchez, J., Heutink, P., Rizzu, P., Sharma, M., Gasser, T., Schneider, S.A., Cookson, M.R., Blauwendraat, C., Craig, D.W., Billingsley, K., Makarious, M.B., Narendra, D.P., Faghri, F., Gibbs, J.R., Hernandez, D.G., Van Keuren-Jensen, K., Shulman, J.M., Iwaki, H., Leonard, H.L., Nalls, M.A., Robak, L., Bras, J., Guerreiro, R., Lubbe, S., Troycoco, T., Finkbeiner, S., Mencacci, N.E., Lungu, C., Singleton, A.B., Scholz, S.W., Reed, X., Uitti, R.J., Ross, O.A., Grenn, F.P., Moore, A., Alcalay, R.N., Wszolek, Z.K., Gan-Or, Z., Rouleau, G.A., Krohn, L., Mufti, K., van Hilten, J.J., Marinus, J., Adarmes-Gómez, A.D., Aguilar, M., Alvarez, I., Alvarez, V., Barrero, F.J., Yarza, J.A.B., Bernal-Bernal, I., Blazquez, M., Bonilla-Toribio, M., Botía, J.A., Boungiorno, M.T., Buiza-Rueda, D., Cámara, A., Carrillo, F., Carrión-Claro, M., Cerdan, D., Clarimón, J., Compta, Y., Diez-Fairen, M., Dols-Icardo, O., Duarte, J., Duran, R., Escamilla-Sevilla, F., Ezquerra, M., Feliz, C., Fernández, M., Fernández-Santiago, R., Garcia, C., García-Ruiz, P., Gómez-Garre, P., Heredia, M.J.G., Gonzalez-Aramburu, I., Pagola, A.G., Hoenicka, J., Infante, J., Jesús, S., Jimenez-Escrig, A., Kulisevsky, J., Labrador-Espinosa, M.A., Lopez-Sendon, J.L., de Munain Arregui, A.L., Macias, D., Torres, I.M., Marín, J., Marti, M.J., Martínez-Castrillo, J.C., Méndez-del-Barrio, C., González, M.M., Mata, M., Mínguez, A., Mir, P., Rezola, E.M., Muñoz, E., Pagonabarraga, J., Pastor, P., Errazquin, F.P., Periñán-Tocino, T., Ruiz-Martínez, J., Ruz, C., Rodriguez, A.S., Sierra, M., Suarez-Sanmartin, E., Tabernero, C., Tartari, J.P., Tejera-Parrado, C., Tolosa, E., Valldeoriola, F., Vargas-González, L., Vela, L., Vives, F., Zimprich, A., Pihlstrom, L., Toft, M., Taba, P., Kõks, S., Hassin-Baer, S., Majamaa, K., Siitonen, A., Tienari, P., Okubadejo, N.U., Ojo, O.O., Shashkin, C., Zharkinbekova, N., Akhmetzhanov, V., Kaishybayeva, G., Karimova, A., Khaibullin, T., Lynch, T.L., Hingorani, A.D., Wood, N.W., Storm, C.S., Kia, D.A., Almramhi, M.M., Bandrés-Ciga, S., Finan, C., Noyce, A.J., Kaiyrzhanov, R., Middlehurst, B., Tan, M., Houlden, H., Morris, H.R., Plun-Favreau, H., Holmans, P., Hardy, J., Trabzuni, D., Quinn, J., Bubb, V., Mok, K.Y., Kinghorn, K.J., Lewis, P., Schreglmann, S.R., Lovering, R., R’Bibo, L., Manzoni, C., Rizig, M., Ryten, M., Guelfi, S., Escott-Price, V., Chelban, V., Foltynie, T., Williams, N., Morrison, K.E., Clarke, C., Harvey, K., Jacobs, B.M., Brice, A., Danjou, F., Lesage, S., Corvol, J-C, Martinez, M., Schulte, C., Brockmann, K., Simón-Sánchez, J., Heutink, P., Rizzu, P., Sharma, M., Gasser, T., Schneider, S.A., Cookson, M.R., Blauwendraat, C., Craig, D.W., Billingsley, K., Makarious, M.B., Narendra, D.P., Faghri, F., Gibbs, J.R., Hernandez, D.G., Van Keuren-Jensen, K., Shulman, J.M., Iwaki, H., Leonard, H.L., Nalls, M.A., Robak, L., Bras, J., Guerreiro, R., Lubbe, S., Troycoco, T., Finkbeiner, S., Mencacci, N.E., Lungu, C., Singleton, A.B., Scholz, S.W., Reed, X., Uitti, R.J., Ross, O.A., Grenn, F.P., Moore, A., Alcalay, R.N., Wszolek, Z.K., Gan-Or, Z., Rouleau, G.A., Krohn, L., Mufti, K., van Hilten, J.J., Marinus, J., Adarmes-Gómez, A.D., Aguilar, M., Alvarez, I., Alvarez, V., Barrero, F.J., Yarza, J.A.B., Bernal-Bernal, I., Blazquez, M., Bonilla-Toribio, M., Botía, J.A., Boungiorno, M.T., Buiza-Rueda, D., Cámara, A., Carrillo, F., Carrión-Claro, M., Cerdan, D., Clarimón, J., Compta, Y., Diez-Fairen, M., Dols-Icardo, O., Duarte, J., Duran, R., Escamilla-Sevilla, F., Ezquerra, M., Feliz, C., Fernández, M., Fernández-Santiago, R., Garcia, C., García-Ruiz, P., Gómez-Garre, P., Heredia, M.J.G., Gonzalez-Aramburu, I., Pagola, A.G., Hoenicka, J., Infante, J., Jesús, S., Jimenez-Escrig, A., Kulisevsky, J., Labrador-Espinosa, M.A., Lopez-Sendon, J.L., de Munain Arregui, A.L., Macias, D., Torres, I.M., Marín, J., Marti, M.J., Martínez-Castrillo, J.C., Méndez-del-Barrio, C., González, M.M., Mata, M., Mínguez, A., Mir, P., Rezola, E.M., Muñoz, E., Pagonabarraga, J., Pastor, P., Errazquin, F.P., Periñán-Tocino, T., Ruiz-Martínez, J., Ruz, C., Rodriguez, A.S., Sierra, M., Suarez-Sanmartin, E., Tabernero, C., Tartari, J.P., Tejera-Parrado, C., Tolosa, E., Valldeoriola, F., Vargas-González, L., Vela, L., Vives, F., Zimprich, A., Pihlstrom, L., Toft, M., Taba, P., Kõks, S., Hassin-Baer, S., Majamaa, K., Siitonen, A., Tienari, P., Okubadejo, N.U., Ojo, O.O., Shashkin, C., Zharkinbekova, N., Akhmetzhanov, V., Kaishybayeva, G., Karimova, A., Khaibullin, T., Lynch, T.L., Hingorani, A.D., and Wood, N.W.
Abstract: Parkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson’s disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson’s disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson’s disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson’s disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson’s disease drug development.
Published: 2021

6. Dentatorubral pallidoluysian atrophy in South Wales

Author: Wardle, M., Majounie, E., Williams, N.M., Rosser, A.E., Morris, H.R., and Robertson, N.P.
Subjects: Genetic markers -- Research, Whites -- Research, Nervous system -- Degeneration, Nervous system -- Genetic aspects, Nervous system -- Development and progression, Nervous system -- Research, Health, Psychology and mental health
Published: 2008

7. Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Author: Guelfi S., D’Sa K., Botía J.A., Vandrovcova J., Reynolds R.H., Zhang D., Trabzuni D., Collado-Torres L., Thomason A., Quijada Leyton P., Gagliano Taliun S.A., Nalls M.A., Noyce A.J., Nicolas A., Cookson M.R., Bandres-Ciga S., Gibbs J.R., Hernandez D.G., Singleton A.B., Reed X., Leonard H., Blauwendraat C., Faghri F., Bras J., Guerreiro R., Tucci A., Kia D.A., Houlden H., Plun-Favreau H., Mok K.Y., Wood N.W., Lovering R., R’Bibo L., Rizig M., Chelban V., Tan M., Morris H.R., Middlehurst B., Quinn J., Billingsley K., Holmans P., Kinghorn K.J., Lewis P., Escott-Price V., Williams N., Foltynie T., Brice A., Danjou F., Lesage S., Corvol J.-C., Martinez M., Giri A., Schulte C., Brockmann K., Simón-Sánchez J., Heutink P., Gasser T., Rizzu P., Sharma M., Shulman J.M., Robak L., Lubbe S., Mencacci N.E., Finkbeiner S., Lungu C., Scholz S.W., Gan-Or Z., Rouleau G.A., Krohan L., van Hilten J.J., Marinus J., Adarmes-Gómez A.D., Bernal-Bernal I., Bonilla-Toribio M., Buiza-Rueda D., Carrillo F., Carrión-Claro M., Mir P., Gómez-Garre P., Jesús S., Labrador-Espinosa M.A., Macias D., Vargas-González L., Méndez-del-Barrio C., Periñán-Tocino T., Tejera-Parrado C., Diez-Fairen M., Aguilar M., Alvarez I., Boungiorno M.T., Carcel M., Pastor P., Tartari J.P., Alvarez V., González M.M., Blazquez M., Garcia C., Suarez-Sanmartin E., Barrero F.J., Rezola E.M., Yarza J.A.B., Pagola A.G., Arregui A.L.M., Ruiz-Martínez J., Cerdan D., Duarte J., Clarimón J., Dols-Icardo O., Infante J., Marín J., Kulisevsky J., Pagonabarraga J., Gonzalez-Aramburu I., Rodriguez A.S., Sierra M., Duran R., Ruz C., Vives F., Escamilla-Sevilla F., Mínguez A., Cámara A., Compta Y., Ezquerra M., Marti M.J., Fernández M., Muñoz E., Fernández-Santiago R., Tolosa E., Valldeoriola F., García-Ruiz P., Heredia M.J.G., Errazquin F.P., Hoenicka J., Jimenez-Escrig A., Martínez-Castrillo J.C., Lopez-Sendon J.L., Torres I.M., Tabernero C., Vela L., Zimprich A., Pihlstrom L., Koks S., Taba P., Majamaa K., Siitonen A., Okubadejo N.U., Ojo O.O., Forabosco P., Walker R., Small K.S., Smith C., Ramasamy A., Hardy J., Weale M.E., and Ryten M.
Subjects: medicine, RNA splicing, phenotype, brain, genotype, Quantitative Trait Loci, genetic analysis, Polymorphism, Single Nucleotide, Article, genetic regulation, mental disease, transcriptomics, quantitative trait locus, expression quantitative trait locus, single nucleotide polymorphism, Humans, genetics, human, reproducibility, Alleles, Neurons, genome-wide association study, human cell, allele, Putamen, Reproducibility of Results, RNA sequencing, Parkinson Disease, gene expression regulation, cell, cohort analysis, neurologic disease, human tissue, schizophrenia, Substantia Nigra, disease incidence, physiology, gene expression, RNA, physiological response, Nervous System Diseases, nerve cell, Transcriptome, nervous system disorder, basal ganglion
Abstract: Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/. © 2020, The Author(s).
Published: 2020

8. Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

Author: Gao, Y. (Yixin), Wang, T. (Ting), Yu, X. (Xinghao), Ferrari, R. (Raffaele), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Brooks, W.S. (William S.), Schofield, P.R. (Peter R.), Halliday, G.M. (Glenda Margaret), Hodges, J.R. (John R.), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (Elizabeth), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (A.), Boada, M. (Mercè), Borroni, B. (Barbara), Padovani, A. (Alessandro), Crane, L.M.A., Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (Roberta), Forloni, G. (Gianluigi), Albani, D. (Diego), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (Elio), Clarimón, J. (Jordi), Lleo, A. (Alberto), Blesa, R. (Rafael), Waldö, M.L. (Maria Landqvist), Nilsson, K. (Karin), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.-Y.R. (Ging-Yuek R.), Mann, D.M.A. (David M. A.), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.J. (Alan J.), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (Michael C.), Pastor, P. (Pau), Razquin, C. (Cristina), Ortega-Cubero, S. (Sara), Alonso, E. (Elena), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), George-Hyslop, P.S. (Peter St), Rossi, G. (Giacomina), Tagliavini, F. (Fabrizio), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (John), Mead, S. (Simon), Danek, A. (Adrian), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (John Q.), Zee, J. (Jill) van der, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Leber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A. (Alexis), Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (Jørgen E.), Hjermind, L.E. (Lena), Riemenschneider, M. (Matthias), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (Wei), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H.R. (Huw R.), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (Ronald C.), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley F.), Parisi, J.E. (Joseph), Seeley, W.W. (William W.), Miller, B.L. (Bruce L.), Karydas, A.M. (Anna M.), Rosen, H. (Howard), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (Harro), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, M. (Massimo), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, C. (Caroline), Pasquier, F. (Florence), Rollin, A. (Adeline), Deramecourt, V. (Vincent), Lebouvier, T. (Thibaud), Kapogiannis, D. (Dimitrios), Ferrucci, L. (Luigi), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Hardy, J. (John), Momeni, P. (Parastoo), Zhao, H. (Huashuo), Zeng, P. (Ping), Gao, Y. (Yixin), Wang, T. (Ting), Yu, X. (Xinghao), Ferrari, R. (Raffaele), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Brooks, W.S. (William S.), Schofield, P.R. (Peter R.), Halliday, G.M. (Glenda Margaret), Hodges, J.R. (John R.), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (Elizabeth), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (A.), Boada, M. (Mercè), Borroni, B. (Barbara), Padovani, A. (Alessandro), Crane, L.M.A., Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (Roberta), Forloni, G. (Gianluigi), Albani, D. (Diego), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (Elio), Clarimón, J. (Jordi), Lleo, A. (Alberto), Blesa, R. (Rafael), Waldö, M.L. (Maria Landqvist), Nilsson, K. (Karin), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.-Y.R. (Ging-Yuek R.), Mann, D.M.A. (David M. A.), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.J. (Alan J.), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (Michael C.), Pastor, P. (Pau), Razquin, C. (Cristina), Ortega-Cubero, S. (Sara), Alonso, E. (Elena), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), George-Hyslop, P.S. (Peter St), Rossi, G. (Giacomina), Tagliavini, F. (Fabrizio), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (John), Mead, S. (Simon), Danek, A. (Adrian), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (John Q.), Zee, J. (Jill) van der, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Leber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A. (Alexis), Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (Jørgen E.), Hjermind, L.E. (Lena), Riemenschneider, M. (Matthias), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (Wei), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H.R. (Huw R.), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (Ronald C.), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley F.), Parisi, J.E. (Joseph), Seeley, W.W. (William W.), Miller, B.L. (Bruce L.), Karydas, A.M. (Anna M.), Rosen, H. (Howard), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (Harro), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, M. (Massimo), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, C. (Caroline), Pasquier, F. (Florence), Rollin, A. (Adeline), Deramecourt, V. (Vincent), Lebouvier, T. (Thibaud), Kapogiannis, D. (Dimitrios), Ferrucci, L. (Luigi), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Hardy, J. (John), Momeni, P. (Parastoo), Zhao, H. (Huashuo), and Zeng, P. (Ping)
Abstract: We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population.
Published: 2020
Full Text: View/download PDF

9. Mass Spectrometry of Glycoprotein Glycans: Glycomics and Glycoproteomics

Author: Dell, A., primary, Chalabi, S., additional, Hitchen, P.G., additional, Jang-Lee, J., additional, Ledger, V., additional, North, S.J., additional, Pang, P.-C., additional, Parry, S., additional, Sutton-Smith, M., additional, Tissot, B., additional, Morris, H.R., additional, Panico, M., additional, and Haslam, S.M., additional
Published: 2007
Full Text: View/download PDF

10. Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability

Author: Reynolds, R.H., Botia, J., Nalls, M.A., Hardy, J., Taliun, S.A.G., Ryten, M., Noyce, A.J., Nicolas, A., Cookson, M.R., Bandres-Ciga, S., Gibbs, J.R., Hernandez, D.G., Singleton, A.B., Reed, X., Leonard, H., Blauwendraat, C., Faghri, F., Bras, J., Guerreiro, R., Tucci, A., Kia, D.A., Houlden, H., Plun-Favreau, H., Mok, K.Y., Wood, N.W., Lovering, R., R'Bibo, L., Rizig, M., Chelban, V., Trabzuni, D., Tan, M., Morris, H.R., Middlehurst, B., Quinn, J., Billingsley, K., Holmans, P., Kinghorn, K.J., Lewis, P., Escott-Price, V., Williams, N., Foltynie, T., Brice, A., Danjou, F., Lesage, S., Corvol, J.C., Martinez, M., Giri, A., Schulte, C., Brockmann, K., Simon-Sanchez, J., Heutink, P., Gasser, T., Rizzu, P., Sharma, M., Shulman, J.M., Robak, L., Lubbe, S., Mencacci, N.E., Finkbeiner, S., Lungu, C., Scholz, S.W., Gan-Or, Z., Rouleau, G.A., Krohan, L., Hilten, J.J. van, Marinus, J., Adarmes-Gomez, A.D., Bernal-Bernal, I., Bonilla-Toribio, M., Buiza-Rueda, D., Carrillo, F., Carrion-Claro, M., Mir, P., Gomez-Garre, P., Jesus, S., Labrador-Espinosa, M.A., Macias, D., Vargas-Gonzalez, L., Mendez-del-Barrio, C., Perinan-Tocino, T., Tejera-Parrado, C., Diez-Fairen, M., Aguilar, M., Alvarez, I., Boungiorno, M.T., Carcel, M., Pastor, P., Tartari, J.P., Alvarez, V., Gonzalez, M.M., Blazquez, M., Garcia, C., Suarez-Sanmartin, E., Barrero, F.J., Rezola, E.M., Yarza, J.A.B., Pagola, A.G., Arregui, A.L.D., Ruiz-Martinez, J., Cerdan, D., Duarte, J., Clarimon, J., Dols-Icardo, O., Infante, J., Marin, J., Kulisevsky, J., Pagonabarraga, J., Gonzalez-Aramburu, I., Rodriguez, A.S., Sierra, M., Duran, R., Ruz, C., Vives, F., Escamilla-Sevilla, F., Minguez, A., Camara, A., Compta, Y., Ezquerra, M., Marti, M.J., Fernandez, M., Munoz, E., Fernandez-Santiago, R., Tolosa, E., Valldeoriola, F., Garcia-Ruiz, P., Heredia, M.J.G., Errazquin, F.P., Hoenicka, J., Jimenez-Escrig, A., Martinez-Castrillo, J.C., Lopez-Sendon, J.L., Torres, I.M., Tabernero, C., Vela, L., Zimprich, A., Pihlstrom, L., Koks, S., Taba, P., Majamaa, K., Siitonen, A., Okubadejo, N.U., Ojo, O.O., Pitcher, T., Anderson, T., Bentley, S., Fowdar, J., Mellick, G., Dalrymple-Alford, J., Henders, A.K., Kassam, I., Montgomery, G., Sidorenko, J., Zhang, F.T., Xue, A.L., Vallerga, C.L., Wallace, L., Wray, N.R., Yang, J., Visscher, P.M., Gratten, J., Silburn, P.A., Halliday, G., Hickie, I., Kwok, J., Lewis, S., Kennedy, M., Pearson, J., Int Parkinsons Dis Genomics, and Syst Genomics Parkinsons Dis
Published: 2019

11. SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease

Author: Fernandez-Santiago, R., Martin-Flores, N., Antonelli, F., Cerquera, C., Moreno, V., Bandres-Ciga, S., Manduchi, E., Tolosa, E., Singleton, A.B., Moore, J.H., Noyce, A.J., Kaiyrzhanov, R., Middlehurst, B., Kia, D.A., Tan, M., Houlden, H., Morris, H.R., Plun-Favreau, H., Holmans, P., Hardy, J., Trabzuni, D., Bras, J., Quinn, J., Mok, K.Y., Kinghorn, K.J., Billingsley, K., Wood, N.W., Lewis, P., Schreglmann, S., Guerreiro, R., Lovering, R., R'Bibo, L., Manzoni, C., Rizig, M., Ryten, M., Guelfi, S., Escott-Price, V., Chelban, V., Foltynie, T., Williams, N., Morrison, K.E., Clarke, C., Brice, A., Danjou, F., Lesage, S., Corvol, J.C., Martinez, M., Schulte, C., Brockmann, K., Simoon-Saanchez, J., Heutink, P., Rizzu, P., Sharma, M., Gasser, T., Nicolas, A., Cookson, M.R., Blauwendraat, C., Craig, D.W., Faghri, F., Gibbs, J.R., Hernandez, D.G., Keuren-Jensen, K. van, Shulman, J.M., Iwaki, H., Leonard, H.L., Nalls, M.A., Robak, L., Lubbe, S., Finkbeiner, S., Mencacci, N.E., Lungu, C., Scholz, S.W., Reed, X., Alcalay, R.N., Gan-Or, Z., Rouleau, G.A., Krohn, L., Hilten, J.J. van, Marinus, J., Adarmes-Goomez, A.D., Aguilar, I., Alvarez, I., Alvarez, V., Barrero, F.J., Yarza, J.A.B., Bernal-Bernal, I., Blazquez, M., Bonilla-Toribio, M., Botia, J.A., Boungiorno, M.T., Buiza-Rueda, D., Camara, A., Carrillo, F., Carrion-Claro, M., Cerdan, D., Clarimon, J., Compta, Y., Casa, B. de la, Diez-Fairen, M., Dols-Icardo, O., Duarte, J., Duran, R., Escamilla-Sevilla, F., Ezquerra, M., Feliz, C., Fernandez, M., Garcia, C., Garcia-Ruiz, P., Gomez-Garre, P., Heredia, M.J.G., Gonzalez-Aramburu, I., Pagola, A.G., Hoenicka, J., Infante, J., Jesus, S., Jimenez-Escrig, A., Kulisevsky, J., Labrador-Espinosa, M.A., Lopez-Sendon, J.L., Arregui, A.L.D., Macias, D., Torres, I.M., Marin, J., Marti, M.J., Martinez-Castrillo, C., Mendez-del-Barrio, C., Gonzalez, M.M., Mata, M., Minguez, A., Mir, P., Rezola, E.M., Munoz, E., Pagonabarraga, J., Pascual-Sedano, B., Pastor, P., Errazquin, F.P., Perinan-Tocino, T., Ruiz-Martinez, J., Ruz, C., Rodriguez, A.S., Sierra, M., Suarez-Sanmartin, E., Tabernero, C., Tartari, J.P., Tejera-Parrado, C., Valldeoriola, F., Vargas-Gonzalez, L., Vela, L., Vives, F., Zimprich, A., Pihlstrom, L., Toft, M., Koks, S., Taba, P., Hassin-Baer, S., Malagelada, C., Int Parkinson's Dis Genomics Conso, Fundació La Marató de TV3, Michael J. Fox Foundation for Parkinson's Research, National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), and Ministerio de Ciencia, Innovación y Universidades (España)
Subjects: 0301 basic medicine, epistasis, Male, Parkinson's disease, very elderly, alpha-synuclein, Alpha‐synuclein, regulatory associated protein of mTOR, Cohort Studies, 0302 clinical medicine, single nucleotide polymorphism, genetics, Age of Onset, Genetics, Aged, 80 and over, Polymorphism, Single Nucleoti, biology, TOR Serine-Threonine Kinases, target of rapamycin kinase, fchsd1 gene, Age at onset, Chromosome Mapping, glycogen synthase kinase 3beta, Parkinson Disease, Middle Aged, cohort analysis, LRRK2, priority journal, Neurology, chromosomal mapping, neuromodulation, mTOR, alpha-Synuclein, Female, age at onset, Signal Transduction, onset age, Adult, MTOR protein, human, protein kinase LKB1, gene locus, Genotype, multifactor dimensionality reduction, SNP, Single-nucleotide polymorphism, rps6ka2 gene, Polymorphism, Single Nucleotide, Risk Assessment, Article, brain function, 03 medical and health sciences, alpha synuclein, medicine, Humans, controlled study, Genetic Predisposition to Disease, human, ddc:610, SNCA protein, human, gene, Mechanistic target of rapamycin, PI3K/AKT/mTOR pathway, mammalian target of rapamycin, Aged, RPTOR, Epistasis, Genetic, Odds ratio, medicine.disease, major clinical study, nervous system diseases, 030104 developmental biology, mTOR signaling, biology.protein, Epistasis, pathology, Neurology (clinical), genetic predisposition, 030217 neurology & neurosurgery
Abstract: Special Issue: Focused Ultrasound in Parkinson's Disease., [Background] Single nucleotide polymorphisms (SNPs) in the α‐synuclein (SNCA ) gene are associated with differential risk and age at onset (AAO) of both idiopathic and Leucine‐rich repeat kinase 2 (LRRK2)‐associated Parkinson's disease (PD). Yet potential combinatory or synergistic effects among several modulatory SNPs for PD risk or AAO remain largely underexplored., [Objectives] The mechanistic target of rapamycin (mTOR ) signaling pathway is functionally impaired in PD. Here we explored whether SNPs in the mTOR pathway, alone or by epistatic interaction with known susceptibility factors, can modulate PD risk and AAO., [Methods] Based on functional relevance, we selected a total of 64 SNPs mapping to a total of 57 genes from the mTOR pathway and genotyped a discovery series cohort encompassing 898 PD patients and 921 controls. As a replication series, we screened 4170 PD and 3014 controls available from the International Parkinson's Disease Genomics Consortium., [Results] In the discovery series cohort, we found a 4‐loci interaction involving STK11 rs8111699, FCHSD1 rs456998, GSK3B rs1732170, and SNCA rs356219, which was associated with an increased risk of PD (odds ratio = 2.59, P, [Conclusions] These findings indicate that genetic variability in the mTOR pathway contributes to SNCA effects in a nonlinear epistatic manner to modulate differential AAO in PD, unraveling the contribution of this cascade in the pathogenesis of the disease. © 2019 International Parkinson and Movement Disorder Society, Funding Information; Fundació la Marató de TV3. Grant Number: 60510; Michael J. Fox Foundation for Parkinson's Research. Grant Numbers: Dyskinesia Challenge 2014, MJF_PPMI_10_001, PI044024; National Institutes of Health. Grant Number: LM010098; Secretaría de Estado de Investigación, Desarrollo e Innovación. Grant Number: SAF2014‐57160R and SAF2017‐88812R.
Published: 2019
Full Text: View/download PDF

12. How to apply the movement disorder society criteria for diagnosis of progressive supranuclear palsy

Author: Grimm, M.-J. Respondek, G. Stamelou, M. Arzberger, T. Ferguson, L. Gelpi, E. Giese, A. Grossman, M. Irwin, D.J. Pantelyat, A. Rajput, A. Roeber, S. van Swieten, J.C. Troakes, C. Antonini, A. Bhatia, K.P. Colosimo, C. van Eimeren, T. Kassubek, J. Levin, J. Meissner, W.G. Nilsson, C. Oertel, W.H. Piot, I. Poewe, W. Wenning, G.K. Boxer, A. Golbe, L.I. Josephs, K.A. Litvan, I. Morris, H.R. Whitwell, J.L. Compta, Y. Corvol, J.-C. Lang, A.E. Rowe, J.B. Höglinger, G.U. for the Movement Disorder Society-endorsed PSP Study Group
Abstract: Background: The Movement Disorder Society criteria for progressive supranuclear palsy define diagnostic allocations, stratified by certainty levels and clinical predominance types. We aimed to study the frequency of ambiguous multiple allocations and to develop rules to eliminate them. Methods: We retrospectively collected standardized clinical data by chart review in a multicenter cohort of autopsy-confirmed patients with progressive supranuclear palsy, to classify them by diagnostic certainty level and predominance type and to identify multiple allocations. Results: Comprehensive data were available from 195 patients. More than one diagnostic allocation occurred in 157 patients (80.5%). On average, 5.4 allocations were possible per patient. We developed four rules for Multiple Allocations eXtinction (MAX). They reduced the number of patients with multiple allocations to 22 (11.3%), and the allocations per patient to 1.1. Conclusions: The proposed MAX rules help to standardize the application of the Movement Disorder Society criteria for progressive supranuclear palsy. © 2019 International Parkinson and Movement Disorder Society. © 2019 International Parkinson and Movement Disorder Society
Published: 2019

13. Mitochondria function associated genes contribute to Parkinson’s Disease risk and later age at onset

Author: Billingsley K.J., Barbosa I.A., Bandrés-Ciga S., Quinn J.P., Bubb V.J., Deshpande C., Botia J.A., Reynolds R.H., Zhang D., Simpson M.A., Blauwendraat C., Gan-Or Z., Gibbs J.R., Nalls M.A., Singleton A., Noyce A., Tucci A., Middlehurst B., Kia D., Tan M., Houlden H., Morris H.R., Plun-Favreau H., Holmans P., Hardy J., Trabzuni D., Bras J., Mok K., Kinghorn K., Wood N., Lewis P., Guerreiro R., Lovering R., R’Bibo L., Rizig M., Escott-Price V., Chelban V., Foltynie T., Williams N., Brice A., Danjou F., Lesage S., Martinez M., Giri A., Schulte C., Brockmann K., Simón-Sánchez J., Heutink P., Rizzu P., Sharma M., Gasser T., Nicolas A., Cookson M., Faghri F., Hernandez D., Shulman J., Robak L., Lubbe S., Finkbeiner S., Mencacci N., Lungu C., Scholz S., Reed X., Leonard H., Rouleau G., Krohan L., van Hilten J., Marinus J., Adarmes-Gómez A., Aguilar M., Alvarez I., Alvarez V., Javier Barrero F., Bergareche Yarza J., Bernal-Bernal I., Blazquez M., Bernal M.B.-T., Boungiorno M., Buiza-Rueda D., Cámara A., Carcel M., Carrillo F., Carrión-Claro M., Cerdan D., Clarimón J., Compta Y., Diez-Fairen M., Dols-Icardo O., Duarte J., Duran R., Escamilla-Sevilla F., Ezquerra M., Fernández M., Fernández-Santiago R., Garcia C., García-Ruiz P., Gómez-Garre P., Heredia M.G., Gonzalez-Aramburu I., Pagola A.G., Hoenicka J., Infante J., Jesús S., Jimenez-Escrig A., Kulisevsky J., Labrador-Espinosa M., Lopez-Sendon J., de Munain Arregui A.L., Macias D., Torres I.M., Marín J., Marti M.J., Martínez-Castrillo J., Méndez-del-Barrio C., Menéndez González M., Mínguez A., Mir P., Rezola E.M., Muñoz E., Pagonabarraga J., Pastor P., Errazquin F.P., Periñán-Tocino T., Ruiz-Martínez J., Ruz C., Rodriguez A.S., Sierra M., Suarez-Sanmartin E., Tabernero C., Tartari J.P., Tejera-Parrado C., Tolosa E., Valldeoriola F., Vargas-González L., Vela L., Vives F., Zimprich A., Pihlstrom L., Taba P., Majamaa K., Siitonen A., Okubadejo N., Ojo O., Ryten M., and Koks S.
Subjects: genotype, Mendelian randomization analysis, CLN8 gene, MUC1 gene, genetic analysis, bioenergy, genetic risk, genetic risk score, Article, ATG14 gene, disorders of mitochondrial functions, MRPS34 gene, degenerative disease, mitochondrial gene, EP300 gene, gene mutation, human, MPI gene, gene, molecular phylogeny, LMBRD1 gene, genome-wide association study, monogenic disorder, mitochondrial dynamics, Parkinson disease, E2F1 gene, mitophagy, CAPRIN2 gene, priority journal, risk factor, LGALS3 gene, disease exacerbation, gene expression, gene ontology, meta analysis
Abstract: Mitochondrial dysfunction has been implicated in the etiology of monogenic Parkinson’s disease (PD). Yet the role that mitochondrial processes play in the most common form of the disease; sporadic PD, is yet to be fully established. Here, we comprehensively assessed the role of mitochondrial function-associated genes in sporadic PD by leveraging improvements in the scale and analysis of PD GWAS data with recent advances in our understanding of the genetics of mitochondrial disease. We calculated a mitochondrial-specific polygenic risk score (PRS) and showed that cumulative small effect variants within both our primary and secondary gene lists are significantly associated with increased PD risk. We further reported that the PRS of the secondary mitochondrial gene list was significantly associated with later age at onset. Finally, to identify possible functional genomic associations we implemented Mendelian randomization, which showed that 14 of these mitochondrial function-associated genes showed functional consequence associated with PD risk. Further analysis suggested that the 14 identified genes are not only involved in mitophagy, but implicate new mitochondrial processes. Our data suggests that therapeutics targeting mitochondrial bioenergetics and proteostasis pathways distinct from mitophagy could be beneficial to treating the early stage of PD. © 2019, The Author(s).
Published: 2019

14. Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia

Author: Bonham, L.W., Steele, N.Z.R., Karch, C.M., Broce, I., Geier, E.G., Wen, N.L., Momeni, P., Hardy, J., Miller, Z.A., Gorno-Tempini, M.L., Hess, C.P., Lewis, P., Miller, B.L., Seeley, W.W., Manzoni, C., Desikan, R.S., Baranzini, S.E., Ferrari, R., Yokoyama, J.S., Hernandez, D.G., Nalls, M.A., Rohrer, J.D., Ramasamy, A., Kwok, J.B.J., Dobson-Stone, C., Schofield, P.R., Halliday, G.M., Hodges, J.R., Piguet, O., Bartley, L., Thompson, E., Haan, E., Hernández, Isabel, Ruiz, A., Boada, M., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N.J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, Diego, Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Clarimón, J., Lleó, Alberto, Blesa, R., Landqvist Waldö, M., Nilsson, K., Nilsson, C., Mackenzie, I.R.A., Hsiung, G.Y.R., Mann, D.M.A., Grafman, J., Morris, C.M., Attems, J., Griffiths, T.D., McKeith, I.G., Thomas, A.J., Pietrini, P., Huey, E.D., Wassermann, E.M., Baborie, A., Jaros, E., Tierney, M.C., Pastor, Pau, Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J.B., Schlachetzki, J.C.M., Uphill, J., Collinge, J., Mead, S., Danek, A., Van Deerlin, V.M., Grossman, M., Trojanowski, J.Q., van der Zee, J., Cruts, M., Van Broeckhoven, C., Cappa, S.F., Leber, I., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, Sandro, Bagnoli, S., Piaceri, I., Nielsen, J.E., Hjermind, L.E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M.N., Fox, N.C., Warren, J.D., Spillantini, M.G., Morris, H.R., Rizzu, P., Heutink, P., Snowden, J.S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A.C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M.E., Smirne, N., Rademakers, R., Baker, M., Dickson, Dennis W., Graff-Radford, N.R., Petersen, R.C., Knopman, D., Josephs, K.A., Boeve, B.F., Parisi, J.E., Karydas, A.M., Rosen, H., van Swieten, J.C., Dopper, E.G.P., Seelaar, H., Pijnenburg, Y.A.L., Scheltens, Philip, Logroscino, G., Capozzo, R., Novelli, V., Puca, A.A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H.H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A.B., Universitat Autònoma de Barcelona, Broce, Iris [0000-0003-4932-1430], Miller, Zachary A. [0000-0002-5991-3053], Lewis, Patrick [0000-0003-4537-0489], Baranzini, Sergio E. [0000-0003-0067-194X], Apollo - University of Cambridge Repository, Int FTD-Genomics Consortium, Neurology, Amsterdam Neuroscience - Neurodegeneration, Divisions, and CCA - Imaging and biomarkers
Subjects: 0301 basic medicine, Aging, Transcription, Genetic, Gene regulatory network, lcsh:Medicine, Genome-wide association study, Apoptosis, Neurodegenerative, Primary progressive aphasia, Cohort Studies, 0302 clinical medicine, 692/617/375/132, Risk Factors, Databases, Genetic, 2.1 Biological and endogenous factors, Gene Regulatory Networks, Protein Interaction Maps, Aetiology, lcsh:Science, Multidisciplinary, Neurodegeneration, Neurodegenerative diseases, article, Frontotemporal lobar degeneration, 631/208/205, Single Nucleotide, Phenotype, ddc, 3. Good health, DNA-Binding Proteins, Frontotemporal Dementia (FTD), 692/617/375/365, Neurological, Medical genetics, 38/39, Engineering sciences. Technology, Transcription, Biotechnology, medicine.medical_specialty, Computational biology, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Databases, Rare Diseases, Genetic, medicine, Aphasia, Acquired Cognitive Impairment, Genetics, Humans, Primary Progressive Nonfluent Aphasia, Polymorphism, Gene, Genetic association study, International FTD-Genomics Consortium, lcsh:R, Human Genome, Neurosciences, medicine.disease, Brain Disorders, 631/208/199, 030104 developmental biology, Gene Expression Regulation, RNA, lcsh:Q, Dementia, Gene expression, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
Published: 2019
Full Text: View/download PDF

15. Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito

Author: Billker, O., Lindo, V., Panico, M., Etienne, A.E., Paxton, T., Dell, A., Rogers, M., Sinden, R.E., and Morris, H.R.
Subjects: Malaria -- Research, Vector control -- Research, Malaria vaccine -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Research has identified xanthurenic acid as being a gametocyte-activating factor in malaria disease transmission. Gametogenesis can be induced in vitro with low concentrations of xanthurenic acid at pH concentrations of between 7.4 and 8.0 to 8.2. Further drugs research will be based on these findings in a bid to stop malaria transmission.
Published: 1998

16. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria

Author: Höglinger, G.U. Respondek, G. Stamelou, M. Kurz, C. Josephs, K.A. Lang, A.E. Mollenhauer, B. Müller, U. Nilsson, C. Whitwell, J.L. Arzberger, T. Englund, E. Gelpi, E. Giese, A. Irwin, D.J. Meissner, W.G. Pantelyat, A. Rajput, A. van Swieten, J.C. Troakes, C. Antonini, A. Bhatia, K.P. Bordelon, Y. Compta, Y. Corvol, J.-C. Colosimo, C. Dickson, D.W. Dodel, R. Ferguson, L. Grossman, M. Kassubek, J. Krismer, F. Levin, J. Lorenzl, S. Morris, H.R. Nestor, P. Oertel, W.H. Poewe, W. Rabinovici, G. Rowe, J.B. Schellenberg, G.D. Seppi, K. van Eimeren, T. Wenning, G.K. Boxer, A.L. Golbe, L.I. Litvan, I. Wenning, G.K. Höglinger, G.U. Morris, H.R. Litvan, I. Kassubek, J. Corvol, J.-C. Whitwell, J.L. Levin, J. van Swieten, J. Bhatia, K.P. Josephs, K.A. Seppi, K. Golbe, L.I. Grossman, M. Dodel, R. Lorenzl, S. van Eimeren, T. Arzberger, T. Müller, U. Poewe, W. Oertel, W.H. Compta, Y. Bordelon, Y. the Movement Disorder Society-endorsed PSP Study Group
Subjects: eye diseases
Abstract: Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective: We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP. Methods: We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds. Results: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions: Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society
Published: 2017

17. Prevalence and age of onset of Parkinson's disease in Cardiff: a community based cross sectional study and meta-analysis

Author: Wickremaratchi, M.M., Perera, D., O'Loghlen, C., Sastry, D., Morgan, E., Jones, A., Edwards, P., Robertson, N.P., Butler, C., Morris, H.R., and Ben-Shlomo, Y.
Subjects: Parkinson's disease -- Distribution, Parkinson's disease -- Demographic aspects, Parkinson's disease -- Research, Age factors in disease -- Research, Observational studies -- Reports, Company distribution practices, Health, Psychology and mental health
Published: 2009

18. Analysis of shared heritability in common disorders of the brain

Author: Anttila, V. Bulik-Sullivan, B. Finucane, H.K. Walters, R.K. Bras, J. Duncan, L. Escott-Price, V. Falcone, G.J. Gormley, P. Malik, R. Patsopoulos, N.A. Ripke, S. Wei, Z. Yu, D. Lee, P.H. Turley, P. Grenier-Boley, B. Chouraki, V. Kamatani, Y. Berr, C. Letenneur, L. Hannequin, D. Amouyel, P. Boland, A. Deleuze, J.-F. Duron, E. Vardarajan, B.N. Reitz, C. Goate, A.M. Huentelman, M.J. Ilyas Kamboh, M. Larson, E.B. Rogaeva, E. George-Hyslop, P.S. Hakonarson, H. Kukull, W.A. Farrer, L.A. Barnes, L.L. Beach, T.G. Yesim Demirci, F. Head, E. Hulette, C.M. Jicha, G.A. Kauwe, J.S.K. Kaye, J.A. Leverenz, J.B. Levey, A.I. Lieberman, A.P. Pankratz, V.S. Poon, W.W. Quinn, J.F. Saykin, A.J. Schneider, L.S. Smith, A.G. Sonnen, J.A. Stern, R.A. Van Deerlin, V.M. Van Eldik, L.J. Harold, D. Russo, G. Rubinsztein, D.C. Bayer, A. Tsolaki, M. Proitsi, P. Fox, N.C. Hampel, H. Owen, M.J. Mead, S. Passmore, P. Morgan, K. Nöthen, M.M. Rossor, M. Lupton, M.K. Hoffmann, P. Kornhuber, J. Lawlor, B. McQuillin, A. Al-Chalabi, A. Bis, J.C. Ruiz, A. Boada, M. Seshadri, S. Beiser, A. Rice, K. Van Der Lee, S.J. De Jager, P.L. Geschwind, D.H. Riemenschneider, M. Riedel-Heller, S. Rotter, J.I. Ransmayr, G. Hyman, B.T. Cruchaga, C. Alegret, M. Winsvold, B. Palta, P. Farh, K.-H. Cuenca-Leon, E. Furlotte, N. Kurth, T. Ligthart, L. Terwindt, G.M. Freilinger, T. Ran, C. Gordon, S.D. Borck, G. Adams, H.H.H. Lehtimäki, T. Wedenoja, J. Buring, J.E. Schürks, M. Hrafnsdottir, M. Hottenga, J.-J. Penninx, B. Artto, V. Kaunisto, M. Vepsäläinen, S. Martin, N.G. Montgomery, G.W. Kurki, M.I. Hämäläinen, E. Huang, H. Huang, J. Sandor, C. Webber, C. Muller-Myhsok, B. Schreiber, S. Salomaa, V. Loehrer, E. Göbel, H. Macaya, A. Pozo-Rosich, P. Hansen, T. Werge, T. Kaprio, J. Metspalu, A. Kubisch, C. Ferrari, M.D. Belin, A.C. Van Den Maagdenberg, A.M.J.M. Zwart, J.-A. Boomsma, D. Eriksson, N. Olesen, J. Chasman, D.I. Nyholt, D.R. Avbersek, A. Baum, L. Berkovic, S. Bradfield, J. Buono, R. Catarino, C.B. Cossette, P. De Jonghe, P. Depondt, C. Dlugos, D. Ferraro, T.N. French, J. Hjalgrim, H. Jamnadas-Khoda, J. Kälviäinen, R. Kunz, W.S. Lerche, H. Leu, C. Lindhout, D. Lo, W. Lowenstein, D. McCormack, M. Møller, R.S. Molloy, A. Ng, P.-W. Oliver, K. Privitera, M. Radtke, R. Ruppert, A.-K. Sander, T. Schachter, S. Schankin, C. Scheffer, I. Schoch, S. Sisodiya, S.M. Smith, P. Sperling, M. Striano, P. Surges, R. Neil Thomas, G. Visscher, F. Whelan, C.D. Zara, F. Heinzen, E.L. Marson, A. Becker, F. Stroink, H. Zimprich, F. Gasser, T. Gibbs, R. Heutink, P. Martinez, M. Morris, H.R. Sharma, M. Ryten, M. Mok, K.Y. Pulit, S. Bevan, S. Holliday, E. Attia, J. Battey, T. Boncoraglio, G. Thijs, V. Chen, W.-M. Mitchell, B. Rothwell, P. Sharma, P. Sudlow, C. Vicente, A. Markus, H. Kourkoulis, C. Pera, J. Raffeld, M. Silliman, S. Perica, V.B. Thornton, L.M. Huckins, L.M. William Rayner, N. Lewis, C.M. Gratacos, M. Rybakowski, F. Keski-Rahkonen, A. Raevuori, A. Hudson, J.I. Reichborn-Kjennerud, T. Monteleone, P. Karwautz, A. Mannik, K. Baker, J.H. O'Toole, J.K. Trace, S.E. Davis, O.S.P. Helder, S.G. Ehrlich, S. Herpertz-Dahlmann, B. Danner, U.N. Van Elburg, A.A. Clementi, M. Forzan, M. Docampo, E. Lissowska, J. Hauser, J. Tortorella, A. Maj, M. Gonidakis, F. Tziouvas, K. Papezova, H. Yilmaz, Z. Wagner, G. Cohen-Woods, S. Herms, S. Julia, A. Rabionet, R. Dick, D.M. Ripatti, S. Andreassen, O.A. Espeseth, T. Lundervold, A.J. Steen, V.M. Pinto, D. Scherer, S.W. Aschauer, H. Schosser, A. Alfredsson, L. Padyukov, L. Halmi, K.A. Mitchell, J. Strober, M. Bergen, A.W. Kaye, W. Szatkiewicz, J.P. Cormand, B. Ramos-Quiroga, J.A. Sánchez-Mora, C. Ribasés, M. Casas, M. Hervas, A. Arranz, M.J. Haavik, J. Zayats, T. Johansson, S. Williams, N. Dempfle, A. Rothenberger, A. Kuntsi, J. Oades, R.D. Banaschewski, T. Franke, B. Buitelaar, J.K. Vasquez, A.A. Doyle, A.E. Reif, A. Lesch, K.-P. Freitag, C. Rivero, O. Palmason, H. Romanos, M. Langley, K. Rietschel, M. Witt, S.H. Dalsgaard, S. Børglum, A.D. Waldman, I. Wilmot, B. Molly, N. Bau, C.H.D. Crosbie, J. Schachar, R. Loo, S.K. McGough, J.J. Grevet, E.H. Medland, S.E. Robinson, E. Weiss, L.A. Bacchelli, E. Bailey, A. Bal, V. Battaglia, A. Betancur, C. Bolton, P. Cantor, R. Celestino-Soper, P. Dawson, G. De Rubeis, S. Duque, F. Green, A. Klauck, S.M. Leboyer, M. Levitt, P. Maestrini, E. Mane, S. Moreno-De-Luca, D. Parr, J. Regan, R. Reichenberg, A. Sandin, S. Vorstman, J. Wassink, T. Wijsman, E. Cook, E. Santangelo, S. Delorme, R. Roge, B. Magalhaes, T. Arking, D. Schulze, T.G. Thompson, R.C. Strohmaier, J. Matthews, K. Melle, I. Morris, D. Blackwood, D. McIntosh, A. Bergen, S.E. Schalling, M. Jamain, S. Maaser, A. Fischer, S.B. Reinbold, C.S. Fullerton, J.M. Guzman-Parra, J. Mayoral, F. Schofield, P.R. Cichon, S. Mühleisen, T.W. Degenhardt, F. Schumacher, J. Bauer, M. Mitchell, P.B. Gershon, E.S. Rice, J. Potash, J.B. Zandi, P.P. Craddock, N. Nicol Ferrier, I. Alda, M. Rouleau, G.A. Turecki, G. Ophoff, R. Pato, C. Anjorin, A. Stahl, E. Leber, M. Czerski, P.M. Cruceanu, C. Jones, I.R. Posthuma, D. Andlauer, T.F.M. Forstner, A.J. Streit, F. Baune, B.T. Air, T. Sinnamon, G. Wray, N.R. MacIntyre, D.J. Porteous, D. Homuth, G. Rivera, M. Grove, J. Middeldorp, C.M. Hickie, I. Pergadia, M. Mehta, D. Smit, J.H. Jansen, R. De Geus, E. Dunn, E. Li, Q.S. Nauck, M. Schoevers, R.A. Beekman, A.T.F. Knowles, J.A. Viktorin, A. Arnold, P. Barr, C.L. Bedoya-Berrio, G. Joseph Bienvenu, O. Brentani, H. Burton, C. Camarena, B. Cappi, C. Cath, D. Cavallini, M. Cusi, D. Darrow, S. Denys, D. Derks, E.M. Dietrich, A. Fernandez, T. Figee, M. Freimer, N. Gerber, G. Grados, M. Greenberg, E. Hanna, G.L. Hartmann, A. Hirschtritt, M.E. Hoekstra, P.J. Huang, A. Huyser, C. Illmann, C. Jenike, M. Kuperman, S. Leventhal, B. Lochner, C. Lyon, G.J. Macciardi, F. Madruga-Garrido, M. Malaty, I.A. Maras, A. McGrath, L. Miguel, E.C. Mir, P. Nestadt, G. Nicolini, H. Okun, M.S. Pakstis, A. Paschou, P. Piacentini, J. Pittenger, C. Plessen, K. Ramensky, V. Ramos, E.M. Reus, V. Richter, M.A. Riddle, M.A. Robertson, M.M. Roessner, V. Rosário, M. Samuels, J.F. Sandor, P. Stein, D.J. Tsetsos, F. Van Nieuwerburgh, F. Weatherall, S. Wendland, J.R. Wolanczyk, T. Worbe, Y. Zai, G. Goes, F.S. McLaughlin, N. Nestadt, P.S. Grabe, H.-J. Depienne, C. Konkashbaev, A. Lanzagorta, N. Valencia-Duarte, A. Bramon, E. Buccola, N. Cahn, W. Cairns, M. Chong, S.A. Cohen, D. Crespo-Facorro, B. Crowley, J. Davidson, M. DeLisi, L. Dinan, T. Donohoe, G. Drapeau, E. Duan, J. Haan, L. Hougaard, D. Karachanak-Yankova, S. Khrunin, A. Klovins, J. Kučinskas, V. Keong, J.L.C. Limborska, S. Loughland, C. Lönnqvist, J. Maher, B. Mattheisen, M. McDonald, C. Murphy, K.C. Nenadic, I. Van Os, J. Pantelis, C. Pato, M. Petryshen, T. Quested, D. Roussos, P. Sanders, A.R. Schall, U. Schwab, S.G. Sim, K. So, H.-C. Stögmann, E. Subramaniam, M. Toncheva, D. Waddington, J. Walters, J. Weiser, M. Cheng, W. Cloninger, R. Curtis, D. Gejman, P.V. Henskens, F. Mattingsdal, M. Oh, S.-Y. Scott, R. Webb, B. Breen, G. Churchhouse, C. Bulik, C.M. Daly, M. Dichgans, M. Faraone, S.V. Guerreiro, R. Holmans, P. Kendler, K.S. Koeleman, B. Mathews, C.A. Price, A. Scharf, J. Sklar, P. Williams, J. Wood, N.W. Cotsapas, C. Palotie, A. Smoller, J.W. Sullivan, P. Rosand, J. Corvin, A. Neale, B.M. The Brainstorm Consortium
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.
Published: 2018

19. Sequence analysis of tau in familial and sporadic progressive supranuclear palsy. (Short Report)

Author: Morris, H.R., Katzenschlager, R., Janssen, J.C., Brown, J.M., Ozansoy, M., Quinn, N., Revesz, T., Rossor, M.N., Daniel, S.E., Wood, N.W., and Lees, A.J.
Subjects: Familial diseases -- Research -- Genetic aspects, Neurofibrils -- Physiological aspects -- Research, Parkinson's disease -- Genetic aspects -- Research, Progressive supranuclear palsy -- Genetic aspects -- Research, Health, Psychology and mental health, Physiological aspects, Research, Genetic aspects
Abstract: Progressive supranuclear palsy (PSP) is a tau deposition neurodegenerative disorder which usually occurs in sporadic form and is associated with a common variant of the tau gene. Rare familial forms [...]
Published: 2002

20. Association between a polymorphism of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene and sporadic Parkinson's disease

Author: Zhang, J, Hattori, N, Leroy, E, Morris, H.R, Kubo, S.-I, Kobayashi, T, Wood, N.W, Polymeropoulos, M.H, and Mizuno, Y
Published: 2000
Full Text: View/download PDF

21. Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing

Author: Jansen, I.E., Ye, H., Heetveld, S., Lechler, M.C., Michels, H., Seinstra, R.I., Lubbe, S.J., Drouet, V., Lesage, S., Majounie, E., Gibbs, J.R., Nalls, M.A., Ryten, M., Botia, J.A., Vandrovcova, J., Simon-Sanchez, J., Castillo-Lizardo, M., Rizzu, P., Blauwendraat, C., Chouhan, A.K., Li, Y., Yogi, P., Amin, N., Duijn, C.M. van, Morris, H.R., Brice, A., Singleton, A.B., David, D.C., Nollen, E.A., Jain, S., Shulman, J.M., Heutink, P., Bloem, B., Post, B., Scheffer, H., Warrenburg, B.P.C. van de, et al., Jansen, I.E., Ye, H., Heetveld, S., Lechler, M.C., Michels, H., Seinstra, R.I., Lubbe, S.J., Drouet, V., Lesage, S., Majounie, E., Gibbs, J.R., Nalls, M.A., Ryten, M., Botia, J.A., Vandrovcova, J., Simon-Sanchez, J., Castillo-Lizardo, M., Rizzu, P., Blauwendraat, C., Chouhan, A.K., Li, Y., Yogi, P., Amin, N., Duijn, C.M. van, Morris, H.R., Brice, A., Singleton, A.B., David, D.C., Nollen, E.A., Jain, S., Shulman, J.M., Heutink, P., Bloem, B., Post, B., Scheffer, H., Warrenburg, B.P.C. van de, and et al.
Abstract: Contains fulltext : 169957.pdf (publisher's version ) (Open Access), BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced alpha-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies.
Published: 2017

22. Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing

Author: Jansen, I. (Iris), Ye, H. (Hui), Heetveld, S. (Sasja), Lechler, M.C. (Marie C.), Michels, H. (Helen), Seinstra, R.I. (Renée I.), Lubbe, S.J. (Steven J.), Drouet, V. (Valérie), Lesage, S. (Suzanne), Majounie, E. (Elisa), Gibbs, J.R. (J.Raphael), Nalls, M.A. (Michael), Ryten, M. (Mina), Botia, J.A. (Juan A.), Vandrovcova, J. (Jana), Simón-Sánchez, J. (Javier), Castillo-Lizardo, M. (Melissa), Rizzu, P. (Patrizia), Blauwendraat, C. (Cornelis), Chouhan, A.K. (Amit K.), Li, Y. (Yarong), Yogi, P. (Puja), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Morris, H.R. (Huw R.), Brice, A. (Alexis), Singleton, A. (Andrew), David, D.C. (Della C.), Nollen, E.A. (Ellen A.), Jain, A. (Ashok), Shulman, J.M., Heutink, P. (Peter), Hernandez, D.G. (Dena), Arepalli, S. (Sampath), Brooks, J. (Janet), Price, R. (Ryan), Nicolas, A. (Aude), Chong, S. (Sean), Cookson, M.R. (Mark), Dillman, A. (Allissa), Moore, M. (Matt), Traynor, B.J. (Bryan), Plagnol, V. (Vincent), Nicholas W Wood, Sheerin, U.-M. (Una-Marie), Jose M Bras, Charlesworth, K. (Kate), Gardner, M. (Mac), Guerreiro, R. (Rita), Trabzuni, D. (Danyah), Hardy, J. (John), Sharma, M., Saad, M. (Mohamad), Javier Simón-Sánchez, Schulte, C. (Claudia), Corvol, J.C. (Jean-Christophe), Dürr, A. (Alexandra), Vidailhet, M. (M.), Sveinbjörnsdóttir, S. (Sigurlaug), Barker, R.A. (Roger), Caroline H Williams-Gray, Ben-Shlomo, Y., Berendse, H.W. (Henk W.), Dijk, K.D. (Karin) van, Berg, D. (Daniela), Brockmann, K., Wurster, K.D. (Kathrin), Mätzler, W. (Walter), Gasser, T. (Thomas), Martinez, M. (Maria), Bie, R.M.A. (Rob) de, Biffi, A. (Alessandro), Velseboer, D. (Daan), Bloem, B.R. (Bastiaan), Post, B. (Bart), Wickremaratchi, M. (Mirdhu), Warrenburg, B. (Bart) van de, Bochdanovits, Z. (Zoltan), Bonin, M. (Malte) von, Pétursson, H. (Hjörvar), Riess, O. (Olaf), Burn, D.J. (David), Lubbe, S. (Steven), Cooper, J.M. (J Mark), McNeill, N.H. (Nathan), Schapira, A. (Anthony), Lungu, C. (Codrin), Chen, H. (Honglei), Dong, J. (Jing), Chinnery, P.F. (Patrick F.), Hudson, G. (Gavin), Clarke, C.E. (Carl E.), Moorby, C. (Catriona), Counsell, C. (Carl), Damier, P. (Philippe), Dartigues, J.-F., Deloukas, P. (Panagiotis), Gray, E. (Emma), Edkins, T. (Ted), Hunt, S.E. (Sarah E.), Potter, S.C. (Simon), Tashakkori-Ghanbaria, A. (Avazeh), Deuschl, G. (Günther), Lorenz, D. (Delia), Dexter, D.T. (David), Durif, F. (Frank), Evans, J. (Jonathan Mark), Langford, C. (Cordelia), Foltynie, T. (Thomas), Goate, A.M. (Alison), Harris, C. (Clare), Hilten, J.J. (Jacobus) van, Hofman, A. (Albert), Hollenbeck, J.R. (John R.), Holton, J.L. (Janice), Hu, M. (Michele), Huang, X. (Xiaohong), Illig, T. (Thomas), Jónsson, P.V. (Pálmi), Lambert, J.-C., O'Sullivan, S.S. (Sean), Revesz, T. (Tamas), Shaw, K. (Karen), Lees, A.J. (Andrew), Lichtner, P. (Peter), Limousin, P. (Patricia), Lopez, G., Escott-Price, V. (Valentina), Pearson, J. (Justin), Williams, N. (Nigel), Mudanohwo, E. (Ese), Perlmutter, J.S. (Joel), Pollak, P. (Pierre), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Sawcer, S.J. (Stephen), Scheffer, H. (Hans), Shoulson, I. (Ira), Shulman, L. (Lee), Smith, C. (Colin), Walker, R. (Robert), Spencer, C.C.A. (Chris C.), Strange, A. (Amy), Stefansson, H. (Hreinn), Bettella, F. (Francesco), Zwart, J-A. (John-Anker), Stockton, J.D. (Joanna D.), Talbot, D., Tanner, C.M. (Carlie), Tison, F. (François), Winder-Rhodes, S. (Sophie), Bhatia, K.P. (Kailash), Jansen, I. (Iris), Ye, H. (Hui), Heetveld, S. (Sasja), Lechler, M.C. (Marie C.), Michels, H. (Helen), Seinstra, R.I. (Renée I.), Lubbe, S.J. (Steven J.), Drouet, V. (Valérie), Lesage, S. (Suzanne), Majounie, E. (Elisa), Gibbs, J.R. (J.Raphael), Nalls, M.A. (Michael), Ryten, M. (Mina), Botia, J.A. (Juan A.), Vandrovcova, J. (Jana), Simón-Sánchez, J. (Javier), Castillo-Lizardo, M. (Melissa), Rizzu, P. (Patrizia), Blauwendraat, C. (Cornelis), Chouhan, A.K. (Amit K.), Li, Y. (Yarong), Yogi, P. (Puja), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Morris, H.R. (Huw R.), Brice, A. (Alexis), Singleton, A. (Andrew), David, D.C. (Della C.), Nollen, E.A. (Ellen A.), Jain, A. (Ashok), Shulman, J.M., Heutink, P. (Peter), Hernandez, D.G. (Dena), Arepalli, S. (Sampath), Brooks, J. (Janet), Price, R. (Ryan), Nicolas, A. (Aude), Chong, S. (Sean), Cookson, M.R. (Mark), Dillman, A. (Allissa), Moore, M. (Matt), Traynor, B.J. (Bryan), Plagnol, V. (Vincent), Nicholas W Wood, Sheerin, U.-M. (Una-Marie), Jose M Bras, Charlesworth, K. (Kate), Gardner, M. (Mac), Guerreiro, R. (Rita), Trabzuni, D. (Danyah), Hardy, J. (John), Sharma, M., Saad, M. (Mohamad), Javier Simón-Sánchez, Schulte, C. (Claudia), Corvol, J.C. (Jean-Christophe), Dürr, A. (Alexandra), Vidailhet, M. (M.), Sveinbjörnsdóttir, S. (Sigurlaug), Barker, R.A. (Roger), Caroline H Williams-Gray, Ben-Shlomo, Y., Berendse, H.W. (Henk W.), Dijk, K.D. (Karin) van, Berg, D. (Daniela), Brockmann, K., Wurster, K.D. (Kathrin), Mätzler, W. (Walter), Gasser, T. (Thomas), Martinez, M. (Maria), Bie, R.M.A. (Rob) de, Biffi, A. (Alessandro), Velseboer, D. (Daan), Bloem, B.R. (Bastiaan), Post, B. (Bart), Wickremaratchi, M. (Mirdhu), Warrenburg, B. (Bart) van de, Bochdanovits, Z. (Zoltan), Bonin, M. (Malte) von, Pétursson, H. (Hjörvar), Riess, O. (Olaf), Burn, D.J. (David), Lubbe, S. (Steven), Cooper, J.M. (J Mark), McNeill, N.H. (Nathan), Schapira, A. (Anthony), Lungu, C. (Codrin), Chen, H. (Honglei), Dong, J. (Jing), Chinnery, P.F. (Patrick F.), Hudson, G. (Gavin), Clarke, C.E. (Carl E.), Moorby, C. (Catriona), Counsell, C. (Carl), Damier, P. (Philippe), Dartigues, J.-F., Deloukas, P. (Panagiotis), Gray, E. (Emma), Edkins, T. (Ted), Hunt, S.E. (Sarah E.), Potter, S.C. (Simon), Tashakkori-Ghanbaria, A. (Avazeh), Deuschl, G. (Günther), Lorenz, D. (Delia), Dexter, D.T. (David), Durif, F. (Frank), Evans, J. (Jonathan Mark), Langford, C. (Cordelia), Foltynie, T. (Thomas), Goate, A.M. (Alison), Harris, C. (Clare), Hilten, J.J. (Jacobus) van, Hofman, A. (Albert), Hollenbeck, J.R. (John R.), Holton, J.L. (Janice), Hu, M. (Michele), Huang, X. (Xiaohong), Illig, T. (Thomas), Jónsson, P.V. (Pálmi), Lambert, J.-C., O'Sullivan, S.S. (Sean), Revesz, T. (Tamas), Shaw, K. (Karen), Lees, A.J. (Andrew), Lichtner, P. (Peter), Limousin, P. (Patricia), Lopez, G., Escott-Price, V. (Valentina), Pearson, J. (Justin), Williams, N. (Nigel), Mudanohwo, E. (Ese), Perlmutter, J.S. (Joel), Pollak, P. (Pierre), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Sawcer, S.J. (Stephen), Scheffer, H. (Hans), Shoulson, I. (Ira), Shulman, L. (Lee), Smith, C. (Colin), Walker, R. (Robert), Spencer, C.C.A. (Chris C.), Strange, A. (Amy), Stefansson, H. (Hreinn), Bettella, F. (Francesco), Zwart, J-A. (John-Anker), Stockton, J.D. (Joanna D.), Talbot, D., Tanner, C.M. (Carlie), Tison, F. (François), Winder-Rhodes, S. (Sophie), and Bhatia, K.P. (Kailash)
Abstract: Background: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. Results: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. Conclusions: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies.
Published: 2017
Full Text: View/download PDF

23. Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation

Author: Kiely, A.P., Ling, H., Asi, Y.T., Kara, E., Proukakis, C., Schapira, A.H., Morris, H.R., Roberts, H.C., Lubbe, S., Limousin, P., Lewis, P.A., Lees, A.J., Quinn, N., Hardy, J., Love, S., Revesz, T., Houlden, H, and Holton, J.L.
Subjects: nervous system diseases
Abstract: BackgroundWe and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson’s disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case.ResultsAll three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant ?-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal ?-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had ?-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated ?-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state.ConclusionsOur characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication.
Published: 2015

24. A genome-wide association study in multiple system atrophy

Author: Sailer, A., Scholz, S.W., Nalls, M.A., Schulte, C., Federoff, M., Price, T.R., Lees, A., Ross, O.A., Dickson, D.W., Mok, K., Mencacci, N.E., Schottlaender, L., Chelban, V., Ling, H., O'Sullivan, S.S, Wood, N.W., Traynor, B.J., Ferrucci, L., Federoff, H.J., Mhyre, T.R., Morris, H.R., Deuschl, G., Quinn, N., Widner, H., Albanese, A., Infante, J., Bhatia, K.P., Poewe, W., Oertel, W., Hoglinger, G.U., Wullner, U., Goldwurm, S., Pellecchia, M.T., Ferreira, J., Tolosa, E., Bloem, B.R., Rascol, O., Meissner, W.G., Hardy, J.A., Revesz, T., Holton, J.L., Gasser, T., Wenning, G.K., Singleton, A.B., Houlden, H., Sailer, A., Scholz, S.W., Nalls, M.A., Schulte, C., Federoff, M., Price, T.R., Lees, A., Ross, O.A., Dickson, D.W., Mok, K., Mencacci, N.E., Schottlaender, L., Chelban, V., Ling, H., O'Sullivan, S.S, Wood, N.W., Traynor, B.J., Ferrucci, L., Federoff, H.J., Mhyre, T.R., Morris, H.R., Deuschl, G., Quinn, N., Widner, H., Albanese, A., Infante, J., Bhatia, K.P., Poewe, W., Oertel, W., Hoglinger, G.U., Wullner, U., Goldwurm, S., Pellecchia, M.T., Ferreira, J., Tolosa, E., Bloem, B.R., Rascol, O., Meissner, W.G., Hardy, J.A., Revesz, T., Holton, J.L., Gasser, T., Wenning, G.K., Singleton, A.B., and Houlden, H.
Abstract: Contains fulltext : 167706.pdf (publisher's version ) (Open Access), OBJECTIVE: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). METHODS: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. RESULTS: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 x 10-6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. CONCLUSIONS: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps.
Published: 2016

25. Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases

Author: Witoelar, A.W., Jansen, I.E., Wang, Y., Desikan, R.S., Gibbs, J.R., Blauwendraat, C., Thompson, W.K., Hernandez, D.G., Djurovic, S., Schork, A.J., Bettella, F., Ellinghaus, D., Franke, A., Lie, B.A., McEvoy, L.K., Karlsen, T.H., Lesage, S., Morris, H.R., Brice, A., Wood, N.W., Heutink, P., Hardy, J., Singleton, A.B., Dale, A.M., Gasser, T., Andreassen, O.A., Sharma, M., Nalls, M.A., Plagnol, V., Sheerin, U.M., Saad, M., Simon-Sanchez, J., Schulte, C., Sveinbjörnsdóttir, S., Arepalli, S., Barker, R.A., Ben-Shlomo, Y., Berendse, H.W., Berg, D., Bhatia, K.P., de Bie, R.M.A., Biffi, A., Bloem, B., Bochdanovits, Z., Bonin, M., Bras, J.M., Brockmann, K., Brooks, J.M., Burn, D.J., Majounie, E., Illig, T., Lichtner, P., Weale, M.E., Neurology, Amsterdam Neuroscience - Neurodegeneration, Human genetics, Hu, M, ANS - Neurodegeneration, ANS - Amsterdam Neuroscience, Intensive Care Medicine, AII - Inflammatory diseases, ANS - Neuroinfection & -inflammation, Graduate School, ACS - Amsterdam Cardiovascular Sciences, and APH - Aging & Later Life
Subjects: 0301 basic medicine, Aging, genetics [Autoimmune Diseases], genetics [Colitis, Ulcerative], Ulcerative, Genome-wide association study, Disease, Neurodegenerative, North American Brain Expression Consortium, Bioinformatics, Arthritis, Rheumatoid, International Parkinson’s Disease Genomics Consortium (IPDGC), 0302 clinical medicine, Crohn Disease, genetics [Parkinson Disease], Risk Factors, Pleiotropy, Rheumatoid, Pleiotropism, 2.1 Biological and endogenous factors, Medicine, genetics [Celiac Disease], Aetiology, Original Investigation, Parkinson's Disease, Genetic Pleiotropy, Parkinson Disease, Colitis, LRRK2, International Parkinson’s Disease Genomics Consortium, Neurological, Cognitive Sciences, Type 1, Biotechnology, genetics [Crohn Disease], Multiple Sclerosis, genetics [Arthritis, Rheumatoid], Clinical Sciences, Human leukocyte antigen, genetics [Psoriasis], Autoimmune Disease, Autoimmune Diseases, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Diabetes Mellitus, Genetics, Humans, Psoriasis, Genetic Predisposition to Disease, ddc:610, Genetic association, Neurology & Neurosurgery, North American Brain Expression Consortium (NABEC), business.industry, Arthritis, Prevention, Inflammatory and immune system, Human Genome, Inflammatory Bowel Disease, genetics [Multiple Sclerosis], Neurosciences, genetics [Diabetes Mellitus, Type 1], Brain Disorders, Celiac Disease, Diabetes Mellitus, Type 1, 030104 developmental biology, Genetic Loci, and United Kingdom Brain Expression Consortium (UKBEC) Investigators, Colitis, Ulcerative, Neurology (clinical), Digestive Diseases, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Importance Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. Objectives To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach. Design, Setting, and Participants Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017. Main Outcomes and Measures The primary outcome was a list of novel loci and their pathways involved in PD and autoimmune diseases. Results Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK , HLA-DRB5 , LRRK2 , and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA , LRRK2 , MAPT , TRIM10 , and SE TD1A in PD. Among the novel genes discovered, WNT3 , KANSL1 , CRHR1 , BOLA2 , and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes in methylation or expression levels of adjacent genes. Conclusions and Relevance The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes. The results may have implications for future therapeutic trials involving anti-inflammatory agents.
Published: 2017
Full Text: View/download PDF

26. Parkinson's disease in GTP cyclohydrolase 1 mutation carriers

Author: Mencacci, N.E. Isaias, I.U. Reich, M.M. Ganos, C. Plagnol, V. Polke, J.M. Bras, J. Hersheson, J. Stamelou, M. Pittman, A.M. Noyce, A.J. Mok, K.Y. Opladen, T. Kunstmann, E. Hodecker, S. Münchau, A. Volkmann, J. Samnick, S. Sidle, K. Nanji, T. Sweeney, M.G. Houlden, H. Batla, A. Zecchinelli, A.L. Pezzoli, G. Marotta, G. Lees, A. Alegria, P. Krack, P. Cormier-Dequaire, F. Lesage, S. Brice, A. Heutink, P. Gasser, T. Lubbe, S.J. Morris, H.R. Taba, P. Koks, S. Majounie, E. Gibbs, J.R. Singleton, A. Hardy, J. Klebe, S. Bhatia, K.P. Wood, N.W.
Subjects: nervous system diseases
Abstract: GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Lossof- function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([123I]N-ω- fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson's disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson's disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson's disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher's exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4-25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson's disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, suggesting that it not only leads to biochemical striatal dopamine depletion and DOPA-responsive dystonia, but also predisposes to nigrostriatal cell loss. Further insight into GCH1-associated pathogenetic mechanisms will shed light on the role of dopamine metabolism in nigral degeneration and Parkinson's disease. © The Author (2014).
Published: 2014

27. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

Author: Nalls, M.A. Pankratz, N. Lill, C.M. Do, C.B. Hernandez, D.G. Saad, M. Destefano, A.L. Kara, E. Bras, J. Sharma, M. Schulte, C. Keller, M.F. Arepalli, S. Letson, C. Edsall, C. Stefansson, H. Liu, X. Pliner, H. Lee, J.H. Cheng, R. Ikram, M.A. Ioannidis, J.P.A. Hadjigeorgiou, G.M. Bis, J.C. Martinez, M. Perlmutter, J.S. Goate, A. Marder, K. Fiske, B. Sutherland, M. Xiromerisiou, G. Myers, R.H. Clark, L.N. Stefansson, K. Hardy, J.A. Heutink, P. Chen, H. Wood, N.W. Houlden, H. Payami, H. Brice, A. Scott, W.K. Gasser, T. Bertram, L. Eriksson, N. Foroud, T. Singleton, A.B. Plagnol, V. Sheerin, U.-M. Simón-Sánchez, J. Lesage, S. Sveinbjörnsdóttir, S. Barker, R. Ben-Shlomo, Y. Berendse, H.W. Berg, D. Bhatia, K. de Bie, R.M.A. Biffi, A. Bloem, B. Bochdanovits, Z. Bonin, M. Bras, J.M. Brockmann, K. Brooks, J. Burn, D.J. Charlesworth, G. Chinnery, P.F. Chong, S. Clarke, C.E. Cookson, M.R. Cooper, J.M. Corvol, J.C. Counsell, C. Damier, P. Dartigues, J.-F. Deloukas, P. Deuschl, G. Dexter, D.T. van Dijk, K.D. Dillman, A. Durif, F. Dürr, A. Edkins, S. Evans, J.R. Foltynie, T. Dong, J. Gardner, M. Gibbs, J.R. Gray, E. Guerreiro, R. Harris, C. van Hilten, J.J. Hofman, A. Hollenbeck, A. Holton, J. Hu, M. Huang, X. Wurster, I. Mätzler, W. Hudson, G. Hunt, S.E. Huttenlocher, J. Illig, T. Jónsson, P.V. Lambert, J.-C. Langford, C. Lees, A. Lichtner, P. Limousin, P. Lopez, G. Lorenz, D. McNeill, A. Moorby, C. Moore, M. Morris, H.R. Morrison, K.E. Mudanohwo, E. O’sullivan, S.S. Pearson, J. Pétursson, H. Pollak, P. Post, B. Potter, S. Ravina, B. Revesz, T. Riess, O. Rivadeneira, F. Rizzu, P. Ryten, M. Sawcer, S. Schapira, A. Scheffer, H. Shaw, K. Shoulson, I. Sidransky, E. Smith, C. Spencer, C.C.A. Stefánsson, H. Bettella, F. Stockton, J.D. Strange, A. Talbot, K. Tanner, C.M. Tashakkori-Ghanbaria, A. Tison, F. Trabzuni, D. Traynor, B.J. Uitterlinden, A.G. Velseboer, D. Vidailhet, M. Walker, R. van de Warrenburg, B. Wickremaratchi, M. Williams, N. Williams-Gray, C.H. Winder-Rhodes, S. Stefánsson, K. Hardy, J. Factor, S. Higgins, D. Evans, S. Shill, H. Stacy, M. Danielson, J. Marlor, L. Williamson, K. Jankovic, J. Hunter, C. Simon, D. Ryan, P. Scollins, L. Saunders-Pullman, R. Boyar, K. Costan-Toth, C. Ohmann, E. Sudarsky, L. Joubert, C. Friedman, J. Chou, K. Fernandez, H. Lannon, M. Galvez-Jimenez, N. Podichetty, A. Thompson, K. Lewitt, P. Deangelis, M. O'brien, C. Seeberger, L. Dingmann, C. Judd, D. Marder, K. Fraser, J. Harris, J. Bertoni, J. Peterson, C. Rezak, M. Medalle, G. Chouinard, S. Panisset, M. Hall, J. Poiffaut, H. Calabrese, V. Roberge, P. Wojcieszek, J. Belden, J. Jennings, D. Marek, K. Mendick, S. Reich, S. Dunlop, B. Jog, M. Horn, C. Uitti, R. Turk, M. Ajax, T. Mannetter, J. Sethi, K. Carpenter, J. Dill, B. Hatch, L. Ligon, K. Narayan, S. Blindauer, K. Abou-Samra, K. Petit, J. Elmer, L. Aiken, E. Davis, K. Schell, C. Wilson, S. Velickovic, M. Koller, W. Phipps, S. Feigin, A. Gordon, M. Hamann, J. Licari, E. Marotta-Kollarus, M. Shannon, B. Winnick, R. Simuni, T. Videnovic, A. Kaczmarek, A. Williams, K. Wolff, M. Rao, J. Cook, M. Fernandez, M. Kostyk, S. Hubble, J. Campbell, A. Reider, C. Seward, A. Camicioli, R. Carter, J. Nutt, J. Andrews, P. Morehouse, S. Stone, C. Mendis, T. Grimes, D. Alcorn-Costa, C. Gray, P. Haas, K. Vendette, J. Sutton, J. Hutchinson, B. Young, J. Rajput, A. Klassen, L. Shirley, T. Manyam, B. Simpson, P. Whetteckey, J. Wulbrecht, B. Truong, D. Pathak, M. Frei, K. Luong, N. Tra, T. Tran, A. Vo, J. Lang, A. Kleiner-Fisman, G. Nieves, A. Johnston, L. So, J. Podskalny, G. Giffin, L. Atchison, P. Allen, C. Martin, W. Wieler, M. Suchowersky, O. Furtado, S. Klimek, M. Hermanowicz, N. Niswonger, S. Shults, C. Fontaine, D. Aminoff, M. Christine, C. Diminno, M. Hevezi, J. Dalvi, A. Kang, U. Richman, J. Uy, S. Sahay, A. Gartner, M. Schwieterman, D. Hall, D. Leehey, M. Culver, S. Derian, T. Demarcaida, T. Thurlow, S. Rodnitzky, R. Dobson, J. Lyons, K. Pahwa, R. Gales, T. Thomas, S. Shulman, L. Weiner, W. Dustin, K. Singer, C. Zelaya, L. Tuite, P. Hagen, V. Rolandelli, S. Schacherer, R. Kosowicz, J. Gordon, P. Werner, J. Serrano, C. Roque, S. Kurlan, R. Berry, D. Gardiner, I. Hauser, R. Sanchez-Ramos, J. Zesiewicz, T. Delgado, H. Price, K. Rodriguez, P. Wolfrath, S. Pfeiffer, R. Davis, L. Pfeiffer, B. Dewey, R. Hayward, B. Johnson, A. Meacham, M. Estes, B. Walker, F. Hunt, V. O'neill, C. Racette, B. Swisher, L. Dijamco, C. Conley, E.D. Dorfman, E. Tung, J.Y. Hinds, D.A. Mountain, J.L. Wojcicki, A. Lew, M. Klein, C. Golbe, L. Growdon, J. Wooten, G.F. Watts, R. Guttman, M. Goldwurm, S. Saint-Hilaire, M.H. Baker, K. Litvan, I. Nicholson, G. Nance, M. Drasby, E. Isaacson, S. Burn, D. Pramstaller, P. Al-Hinti, J. Moller, A. Sherman, S. Roxburgh, R. Slevin, J. Perlmutter, J. Mark, M.H. Huggins, N. Pezzoli, G. Massood, T. Itin, I. Corbett, A. Chinnery, P. Ostergaard, K. Snow, B. Cambi, F. Kay, D. Samii, A. Agarwal, P. Roberts, J.W. Higgins, D.S. Molho, E. Rosen, A. Montimurro, J. Martinez, E. Griffith, A. Kusel, V. Yearout, D. Factor, S. Zabetian, C. Clark, L.N. Liu, X. Lee, J.H. Cheng Taub, R. Louis, E.D. Cote, L.J. Waters, C. Ford, B. Fahn, S. Vance, J.M. Beecham, G.W. Martin, E.R. Nuytemans, K. Pericak-Vance, M.A. Haines, J.L. Destefano, A. Seshadri, S. Choi, S.H. Frank, S. Bis, J.C. Psaty, B.M. Rice, K. Longstreth, W.T., Jr. Ton, T.G.N. Jain, S. van Duijn, C.M. Uitterlinden, A.G. Verlinden, V.J. Koudstaal, P.J. Singleton, A. Cookson, M. Gibbs, J.R. Hernandez, D. Nalls, M. Zonderman, A. Ferrucci, L. Johnson, R. Longo, D. O'brien, R. Traynor, B. Troncoso, J. van der Brug, M. Zielke, R. Weale, M. Ramasamy, A. Dardiotis, E. Tsimourtou, V. Spanaki, C. Plaitakis, A. Bozi, M. Stefanis, L. Vassilatis, D. Koutsis, G. Panas, M. Hadjigeorgiou, G.M. Lunnon, K. Lupton, M. Powell, J. Parkkinen, L. Ansorge, O. International Parkinson's Disease Genomics Consortium (IPDGC) Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI) 23andMe GenePD NeuroGenetics Research Consortium (NGRC) Hussman Institute of Human Genomics (HIHG) The Ashkenazi Jewish Dataset Investigator Cohorts for Health Aging Research in Genetic Epidemiology (CHARGE) North American Brain Expression Consortium (NABEC) United Kingdom Brain Expression Consortium (UKBEC) Greek Parkinson's Disease Consortium Alzheimer Genetic Analysis Group
Abstract: We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10-16). We also show six risk loci associated with proximal gene expression or DNA methylation. © 2014 Nature America, Inc. All rights reserved.
Published: 2014

28. Variation in recent onset Parkinson’s disease: implications for pre-motor detection

Author: Swallow, D.M.A., primary, Lawton, M.A., additional, Grosset, K.A., additional, Malek, N., additional, Smith, C.R., additional, Bajaj, N., additional, Barker, R.A., additional, Ben-Shlomo, Y., additional, Burn, D.J., additional, Foltynie, T., additional, Morris, H.R., additional, Williams, N., additional, Wood, N.W., additional, and Grosset, D.G., additional
Published: 2015
Full Text: View/download PDF

29. Cardiovascular risk and statin use in recent onset Parkinson's disease

Author: Swallow, D.M.A., primary, Lawton, M.A., additional, Grosset, K.A., additional, Malek, N., additional, Bajaj, N., additional, Barker, R.A., additional, Ben-Shlomo, Y., additional, Burn, D.J., additional, Foltynie, T., additional, Morris, H.R., additional, Williams, N., additional, Wood, N.W., additional, and Grosset, D.G., additional
Published: 2015
Full Text: View/download PDF

30. Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

Author: Mencacci, N.E., Isaias, I.U., Reich, M.M., Ganos, C., Plagnol, V., Polke, J.M., Bras, J., Hersheson, J., Stamelou, M., Pittman, A.M., Noyce, A.J., Mok, K.Y., Opladen, T., Kunstmann, E., Hodecker, S., Münchau, A., Volkmann, J., Samnick, S., Sidle, K., Nanji, T., Sweeney, M.G., Houlden, H., Batla, A., Zecchinelli, A.L., Pezzoli, G., Marotta, G., Lees, A., Alegria, P., Krack, P., Cormier-Dequaire, F., Lesage, S., Brice, A., Heutink, P., Gasser, T., Lubbe, S.J., Morris, H.R., Taba, P., Kõks, S., Majounie, E., Raphael Gibbs, J., Singleton, A., Hardy, J., Klebe, S., Bhatia, K.P., Wood, N.W., Mencacci, N.E., Isaias, I.U., Reich, M.M., Ganos, C., Plagnol, V., Polke, J.M., Bras, J., Hersheson, J., Stamelou, M., Pittman, A.M., Noyce, A.J., Mok, K.Y., Opladen, T., Kunstmann, E., Hodecker, S., Münchau, A., Volkmann, J., Samnick, S., Sidle, K., Nanji, T., Sweeney, M.G., Houlden, H., Batla, A., Zecchinelli, A.L., Pezzoli, G., Marotta, G., Lees, A., Alegria, P., Krack, P., Cormier-Dequaire, F., Lesage, S., Brice, A., Heutink, P., Gasser, T., Lubbe, S.J., Morris, H.R., Taba, P., Kõks, S., Majounie, E., Raphael Gibbs, J., Singleton, A., Hardy, J., Klebe, S., Bhatia, K.P., and Wood, N.W.
Abstract: GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson’s disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson’s disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson’s disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher’s exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4–25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson’s disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, sugges
Published: 2014

31. Genetic comorbidities in Parkinson's disease

Author: Nalls, M.A., Saad, M., Noyce, A.J., Keller, M.F., Schrag, A., Bestwick, J.P., Traynor, B.J., Gibbs, J.R., Hernandez, D.G., Cookson, M.R., Morris, H.R., Williams, N., Gasser, T., Heutink, P., Wood, N., Hardy, J., Martinez, M., Singleton, A.B., Bloem, B.R., Post, B., Scheffer, H., Warrenburg, B.P.C. van de, et al., Nalls, M.A., Saad, M., Noyce, A.J., Keller, M.F., Schrag, A., Bestwick, J.P., Traynor, B.J., Gibbs, J.R., Hernandez, D.G., Cookson, M.R., Morris, H.R., Williams, N., Gasser, T., Heutink, P., Wood, N., Hardy, J., Martinez, M., Singleton, A.B., Bloem, B.R., Post, B., Scheffer, H., Warrenburg, B.P.C. van de, and et al.
Abstract: Contains fulltext : 138086.pdf (publisher's version ) (Open Access)
Published: 2014

32. PURIFICATION AND COMPARISON OF SLOW-REACTING SUBSTANCES FROM HUMAN, GUINEA-PIG AND RAT

Author: Piper, Priscilla J., primary, Tippins, J.R., additional, Morris, H.R., additional, and Taylor, G.W., additional
Published: 1978
Full Text: View/download PDF

33. SGCZ mutations are unlikely to be associated with myoclonus dystonia

Author: Peall, K.J., primary, Ritz, K., additional, Waite, A.J., additional, Groen, J.L., additional, Morris, H.R., additional, Baas, F., additional, Blake, D.J., additional, and Tijssen, M.A.J., additional
Published: 2014
Full Text: View/download PDF

34. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease

Author: Holmans, P., Moskvina, V., Jones, L., Sharma, M., Vedernikov, A., Buchel, F., Sadd, M., Bras, J.M., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Gibbs, J.R., Schulte, C., Durr, A., Guerreiro, R., Hernandez, D., Brice, A., Stefansson, H., Majamaa, K., Gasser, T., Heutink, P., Wood, N.W., Martinez, M., Singleton, A.B., Nalls, M.A., Hardy, J., Morris, H.R., Williams, N.M., Bloem, B., Post, B., Warrenburg, B.P.C. van de, Ravina, B., Shoulson, I., et al., Holmans, P., Moskvina, V., Jones, L., Sharma, M., Vedernikov, A., Buchel, F., Sadd, M., Bras, J.M., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Gibbs, J.R., Schulte, C., Durr, A., Guerreiro, R., Hernandez, D., Brice, A., Stefansson, H., Majamaa, K., Gasser, T., Heutink, P., Wood, N.W., Martinez, M., Singleton, A.B., Nalls, M.A., Hardy, J., Morris, H.R., Williams, N.M., Bloem, B., Post, B., Warrenburg, B.P.C. van de, Ravina, B., Shoulson, I., and et al.
Abstract: Item does not contain fulltext, Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1-2% in people >60 and 3-4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 x 10(-16)) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the 'regulation of leucocyte/lymphocyte activity' and also 'cytokine-mediated signalling' as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated.
Published: 2013

35. Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease

Author: Keller, M.F., Saad, M., Bras, J., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Buchel, F., Sharma, M., Gibbs, J.R., Schulte, C., Moskvina, V., Durr, A., Holmans, P., Kilarski, L.L., Guerreiro, R., Hernandez, D.G., Brice, A., Ylikotila, P., Stefansson, H., Majamaa, K., Morris, H.R., Williams, N., Gasser, T., Heutink, P., Wood, N.W., Hardy, J., Martinez, M., Singleton, A.B., Nalls, M.A., Donnelly, P., Bloem, B., et al., Keller, M.F., Saad, M., Bras, J., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Buchel, F., Sharma, M., Gibbs, J.R., Schulte, C., Moskvina, V., Durr, A., Holmans, P., Kilarski, L.L., Guerreiro, R., Hernandez, D.G., Brice, A., Ylikotila, P., Stefansson, H., Majamaa, K., Morris, H.R., Williams, N., Gasser, T., Heutink, P., Wood, N.W., Hardy, J., Martinez, M., Singleton, A.B., Nalls, M.A., Donnelly, P., Bloem, B., and et al.
Abstract: Item does not contain fulltext, Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17-38, P = 8.08E - 08) phenotypic variance associated with all types of PD, 15% (95% CI -0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17-44, P = 1.34E - 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered.
Published: 2012

36. Case control analysis of repeat expansion size in ataxia

Author: Majounie, E., primary, Wardle, M., additional, Muzaimi, M., additional, Cross, W.C., additional, Robertson, N.P., additional, Williams, N.M., additional, and Morris, H.R., additional
Published: 2007
Full Text: View/download PDF

37. Clinical grand round: A rapidly progressive pyramidal and extrapyramidal syndrome with a supranuclear gaze palsy

Author: Morris, H.R., primary, Bronstein, Adolfo M., additional, Shaw, Christopher E., additional, Lees, Andrew J., additional, and Love, S., additional
Published: 2005
Full Text: View/download PDF

38. Strong association of theSaitohingene Q7 variant with progressive supranuclear palsy

Author: de Silva, R., primary, Hope, A., additional, Pittman, A., additional, Weale, M.E., additional, Morris, H.R., additional, Wood, N.W., additional, and Lees, A.J., additional
Published: 2003
Full Text: View/download PDF

39. Tau exon 10 +16 mutation FTDP-17 presenting clinically as sporadic young onset PSP

Author: Morris, H.R., primary, Osaki, Y., additional, Holton, J., additional, Lees, A.J., additional, Wood, N.W., additional, Revesz, T., additional, and Quinn, N., additional
Published: 2003
Full Text: View/download PDF

40. Association between a polymorphism of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene and sporadic Parkinson's disease [Parkinsonism Relat Disord 6 (4) (2000) 195–197]

Author: Zhang, J, primary, Hattori, N, additional, Leroy, E, additional, Morris, H.R, additional, Kubo, S.-I, additional, Kobayashi, T, additional, Wood, N.W, additional, Polymeropoulous, M.H, additional, and Mizuno, Y, additional
Published: 2002
Full Text: View/download PDF

41. Large scale mapping of oligosaccharide heterogeneity (glycomes)

Author: Dell, A., primary, Sutton-Smith, M., additional, Panico, M., additional, North, S., additional, and Morris, H.R., additional
Published: 2002
Full Text: View/download PDF

42. Differences Between Neonates and Adults in Tissue-Type-Plasminogen Activator (t-PA)-Catalyzed Plasminogen Activation With Various Effectors and in Carbohydrate Sequences of Fibrinogen Chains

Author: Ries, M., primary, Easton, R.L., additional, Longstaff, C., additional, Zenker, M., additional, Corran, P.H., additional, Morris, H.R., additional, Dell, A., additional, and Gaffney, P.J., additional
Published: 2001
Full Text: View/download PDF

43. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype

Author: Houlden, H., primary, Baker, M., additional, Morris, H.R., additional, MacDonald, N., additional, Pickering-Brown, S., additional, Adamson, J., additional, Lees, A.J., additional, Rossor, M.N., additional, Quinn, N.P., additional, Kertesz, A., additional, Khan, M.N., additional, Hardy, J., additional, Lantos, P.L., additional, St. George-Hyslop, P., additional, Munoz, D.G., additional, Mann, D., additional, Lang, A.E., additional, Bergeron, C., additional, Bigio, E.H., additional, Litvan, I., additional, Bhatia, K.P., additional, Dickson, D., additional, Wood, N.W., additional, and Hutton, M., additional
Published: 2001
Full Text: View/download PDF

44. Multiple system atrophy/progressive supranuclear palsy: -Synuclein, synphilin, tau, and APOE

Author: Morris, H.R., primary, Vaughan, J.R., additional, Datta, S.R., additional, Bandopadhyay, R., additional, Rohan de Silva, H.A., additional, Schrag, A., additional, Cairns, N.J., additional, Burn, D., additional, Nath, U., additional, Lantos, P.L., additional, Daniel, S., additional, Lees, A.J., additional, Quinn, N.P., additional, and Wood, N.W., additional
Published: 2000
Full Text: View/download PDF

45. A rapid mass spectrometric strategy suitable for the investigation of glycan alterations in knockout mice

Author: Sutton-Smith, M, primary, Morris, H.R, additional, and Dell, A, additional
Published: 2000
Full Text: View/download PDF

46. Late-onset cytoplasmic body myopathy resembling myotonic dystrophy

Author: Morris, H.R., primary, Landon, D., additional, Morgan-Hughes, J., additional, and Brown, P., additional
Published: 1999
Full Text: View/download PDF

47. Increased Concentrations of Nitric Oxide Synthase Inhibitor(S) in Plasma Samples of Spontaneously Hypertensive Rats

Author: Khan, N.S., primary, Alagbhand-Zadeh, J., additional, Mehdizadeh, S., additional, Holland, S., additional, Das, I., additional, de Belleroche, J., additional, Etienne, A., additional, Panico, M., additional, Tippins, J., additional, Morris, H.R., additional, and de Wardener, H.E., additional
Published: 1998
Full Text: View/download PDF

48. Structural studies of a novel type of pentaantennary large glycan unit in the fertilization-associated carbohydrate-rich glycopeptide isolated from the fertilized eggs of Oryzias latipes.

Author: Taguchi, T., primary, Seko, A., additional, Kitajima, K., additional, Muto, Y., additional, Inoue, S., additional, Khoo, K.H., additional, Morris, H.R., additional, Dell, A., additional, and Inoue, Y., additional
Published: 1994
Full Text: View/download PDF

49. O-glycosylation mimics N-glycosylation in the 16-kDa fragment of bovine pro-opiomelanocortin. The major O-glycan attached to Thr-45 carries SO4-4GalNAc beta 1-4GlcNAc beta 1-, which is the archetypal non-reducing epitope in the N-glycans of pituitary glycohormones.

Author: Siciliano, R.A., primary, Morris, H.R., additional, Bennett, H.P., additional, and Dell, A., additional
Published: 1994
Full Text: View/download PDF

50. Studies on the carbohydrate moiety and on the biosynthesis of rat C-reactive protein

Author: Sambasivam, H., primary, Rassouli, M., additional, Murray, R.K., additional, Nagpurkar, A., additional, Mookerjea, S., additional, Azadi, P., additional, Dell, A., additional, and Morris, H.R., additional
Published: 1993
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

Database

Publisher

142 results on '"Morris H.R."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources