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1. Trial of Deferiprone in Parkinson’s Disease

Author

Devos, David, Labreuche, Julien, Dušek, Petr, Post, Bart, Bloem, Bastiaan R, Berg, Daniela, Maetzler, Walter, Otto, Markus, Habert, Marie-Odile, Lehericy, Stéphane, Ferreira, Joaquim, Dodel, Richard, Rascol, Olivier, Tranchant, Christine, Eusebio, Alexandre, Thobois, Stéphane, Marques, Ana-Raquel, Meissner, Wassilios G, Ory-Magne, Fabienne, Walter, Uwe, de Bie, Rob M A, Gago, Miguel, Vilas, Dolores, Corvol, Jean-Christophe, Kulisevsky, Jaime, Januario, Cristina, Coelho, Miguel V S, Behnke, Stefanie, Worth, Paul, Seppi, Klaus, Ouk, Thavarak, Potey, Camille, Leclercq, Céline, Viard, Romain, Duhamel, Alain, Kuchcinski, Gregory, Lopes, Renaud, Pruvo, Jean-Pierre, Pigny, Pascal, Garçon, Guillaume, Simonin, Ophélie, Carpentier, Jessica, Rolland, Anne-Sophie, Nyholm, Dag, Scherfler, Christoph, Guyon Delannoy, Pauline, Mangin, Jean-François, Chupin, Marie, Bordet, Régis, Dexter, David T, Fradette, Caroline, Spino, Michael, Tricta, Fernando, Ayton, Scott, Bush, Ashley I, Devedjian, Jean-Christophe, Poewe, Werner, Duce, James A, Cabantchik, Ioav, Defebvre, Luc, Deplanque, Dominique, Moreau, Caroline, Group, FAIRPARK-II Study, Compta, Yaroslau, Pavese, Nicola, Růžička, Evžen, Basenau, Sandra, Beliveau, Vincent, Benchetrit, Eve, Best, Laura, Bloem, Bas, Bonicel, Robin, Boraud, T., Bordet, Regis, Bouca, Raquel, Bourdain, Frédéric, Bouzas, Jimena, Brefel-Courbon, Christine, Bubenheim, Michael, Burn, David, Bush, Ashley I, Cabantchik, Ioav, Calvas, Fabienne, Cámara, Ana, Campolongo, Antonia, Carrière, Nicolas, Chaigneau, Véronique, Matthieu, Collin, Compta, Yaroslau, Connelly, John, Cormier-Dequaire, Florence, Cranston, Amy, Dean, Rory, De Marzi, Roberto, Degos, Bertrand, Demotes, Jacques, Dellapina, Estelle, Deplanque, Dominique, Devedjian, Jean-Christophe, Devos, David, Dexter, David, Dodel, Richard, Dongmo, Carole, Duce, James, Duhamel, Alain, Dupouy, Julia, Dusek, Petr, El Mountassir, Fouzia, Eyvrard, Frédéric, Fernández, Manel, Ferreira, Joaquim, Forni, Gian Luca, Foster, Victoria, Foubert-Samier, Alexandra, Fradette, Caroline, Fréville, Laëtitia, Galitzky, Monique, Gaudebout, Cecile, Gelé, Patrick, Giladi, Nir, Grabli, David, Gleixner, Franck, Grolez, Guillaume, Guyon, Pauline, Habert, Marie-Odile, Harroch, Estelle, Hartmann, Andreas, Hirsch, Denise, Hisbergues, Michael, Hobert, Markus A, Hopfner, Franziska, Jurado, Camille, Kaiser, Andreas, Keen, Gill, Klaus, Seppi, Kouassi, Nadège, Labreuch, Julien, Lacomblez, Lucette, Lagha Boukbiza, Ouhaid, Lanthaler, Barbara, Lechatellier, Gilles, Le Forestier, Nadine, Lehmann, Fred, Lloret, Teresa, Le Naour, J., Le Toullec, Benjamin, Locatelli, Maxime, Löhle, Matthias, Lomeña, F., Longato, Nadine, Lützen, Ulf, McNichol, Ann, Maetzler, Corina, Maetzler, Walter, Mahlknecht, Philipp, Mangone, Graziella, Marín-Lahoz, Juan, Mariani, Louise-Laure, Marques, Ana, Matei, Mihaela, Matthias, Löhle, Maucourt Bacchi, Emilie, Meissner, Wassilios, Michon, Amelie, Moreau, Caroline, Nardocci, Nardo, Nosal, Florence, Nyholm, Dag, Oeckl, Patrick, Oravska, Irena, Ory, Fabienne, Otto, Markus, Ouk, Thavarak, Pagonabarraga, Javier, Pascual-Sedano, Berta, Peball, Marina, Phillips, Clélie, Pineau, Fanny, Planellas, Lluís, Pop-Ilieva, Chiesi, Rabier, Aurélie, Olivier, D., Riedel, Christian, Rodrigues, Maura, Roullet-Solignac, Isabelle, Rose, Christian, Rozova, Anna, Růžička, Evžen, Salis, Alexandra, Schäffer, Eva, Scherfler, Christoph, Schiefermeier, Natalia, Seppi, Klaus, Smagghe, Delphine, Silva, Tânia, Silva, Pedro, Socha, Julie, Souyris, Corinne, Spampinato, Umberto, Spino, Michael, Steel, Alison, Sweta, Bajaj, Thalamas, Claire, Teodor, Danaila, Teresa, Anna, Tison, François, Tolosa, Eduardo, Tricta, Fernando, Trifirò Trifirò, Gianluca, Vidailhet, Marie, Wang, Yi, Werkmann, Mario, Yilmas, Rezzak, You, Hana, Zeuner, Kirsten, Defebvre, Luc, Rascol, Olivier, Tranchant, Christine, Eusebio, Alexandre, Thobois, Stéphane, Corvol, Jean-Christophe, Durif, Franck, Meissner, Wassilos, Yaroslau, Compta, Vilas, Dolores, Kulisevsky, Jaime, Poewe, Werner, Ruzicka, Evzen, Gago, Miguel, Januario, Cristina, Vilhena Soares Coelho, Miguel, Berg, Daniela, Behnke, Stefanie, Walter, Uwe, Worth, Paul, Pavese, Nicola, Post, Bart, de Bie, Rob M A, Abbruzzese, Giovanni, Accart, Bertrand, Allain, Marie-Anne, Anheim, Mathieu, Ardigo, Diego, Aracil-Bolaños, Ignacio, Baba, Paul, Bakker, Martijn, Balzer-Geldsetzer, Monika, Bargalló, Núria, Barone, Paolo, Neurology, ANS - Neurodegeneration, and APH - Aging & Later Life

Subjects
administration & dosage [Deferiprone], Dopamine, Dopamine Agents, Medizin, Administration, Oral, Levodopa, Antiparkinson Agents, therapeutic use [Dopamine Agents], therapeutic use [Deferiprone], Deferiprone, metabolism [Iron], adverse effects [Deferiprone], Geriatrics/Aging, Parkinson Disease, General Medicine, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Hematology/Oncology, chemistry [Substantia Nigra], adverse effects [Dopamine Agents], Disease Progression, administration & dosage [Dopamine Agents], physiopathology [Parkinson Disease], adverse effects [Iron Chelating Agents], Neutropenia, analysis [Iron], administration & dosage [Antiparkinson Agents], Iron, metabolism [Parkinson Disease], Neurology/Neurosurgery, therapeutic use [Levodopa], Iron Chelating Agents, pharmacology [Iron Chelating Agents], Double-Blind Method, adverse effects [Antiparkinson Agents], Genetics, diagnostic imaging [Substantia Nigra], metabolism [Substantia Nigra], Humans, ddc:610, diagnostic imaging [Brain], therapeutic use [Antiparkinson Agents], Brain Chemistry, pharmacology [Antiparkinson Agents], therapeutic use [Iron Chelating Agents], Hematology/Oncology General, chemically induced [Neutropenia], pharmacology [Deferiprone], drug therapy [Parkinson Disease], administration & dosage [Iron Chelating Agents], Geriatrics/Aging General, pharmacology [Dopamine Agents], drug effects [Substantia Nigra], Neuroscience
Abstract

Contains fulltext : 287484.pdf (Publisher’s version ) (Open Access) BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P

Published
2022
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3. Level I PD-MCI Using Global Cognitive Tests and the Risk for Parkinson's Disease Dementia

Author

Boel, Judith A, De Bie, Rob MA, Schmand, Ben A, Dalrymple-Alford, John C, Marras, Connie, Adler, Charles H, Goldman, Jennifer G, Tröster, Alexander I, Burn, David J, Litvan, Irene, Geurtsen, Gert J, MDS Study Group Mild Cognitive Impairment In Parkinson's Disease, de Bie, Rob MA [0000-0001-5267-0784], Adler, Charles H [0000-0002-1045-2743], Geurtsen, Gert J [0000-0002-2508-340X], and Apollo - University of Cambridge Repository

Subjects
Aging, Parkinson's Disease, Parkinson's disease, global cognitive tests, Neurosciences, Neurodegenerative, Brain Disorders, mild cognitive impairment, Clinical Research, Neurological, Acquired Cognitive Impairment, diagnostic accuracy, Dementia, MDS Study Group Mild Cognitive Impairment in Parkinson's Disease, dementia
Abstract

BackgroundThe criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown.MethodsThe MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n=467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD.ResultsPD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR=2.57, P=0.001; HR=4.14, P=&nbsp

Published
2022

4. European Academy of Neurology/Movement Disorder Society-European Section Guidelines on Pallidotomy for Parkinson's Disease: Let's Be Accurate

Author

Hariz, Marwan, Bronstein, Jeff M, Cosgrove, G Rees, de Bie, Rob M A, DeLong, Mahlon R, Gross, Robert E, Krack, Paul, Krauss, Joachim K, Lang, Anthony E, Lees, Andrew J, Lozano, Andres M, Obeso, José A, Schuurman, P Richard, Vitek, Jerold L, Neurosurgery, Neurology, ANS - Neurodegeneration, and ANS - Systems & Network Neuroscience

Subjects
610 Medicine & health, 610 Medizin und Gesundheit
Published
2022
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7. Additional file 1 of Comparison of [18F]-FDOPA PET and [123I]-FP-CIT SPECT acquired in clinical practice for assessing nigrostriatal degeneration in patients with a clinically uncertain parkinsonian syndrome

Author

Wallert, Elon, Letort, Erwann, van der Zant, Friso, Winogrodzka, Ania, Berendse, Henk, Beudel, Martijn, de Bie, Rob, Booij, Jan, Raijmakers, Pieter, and van de Giessen, Elsmarieke

Abstract

Additional file 1. Supplemental material includes supplementary methods and supplementary figure S1 and S2.

Published
2022
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8. Supplemental Material, sj-docx-1-gsj-10.1177_21925682211034500 - Instrumentation Techniques to Prevent Proximal Junctional Kyphosis and Proximal Junctional Failure in Adult Spinal Deformity Correction: A Systematic Review of Clinical Studies

Author

Vercoulen, Timon F. G., Doodkorte, Remco J. P., Roth, Alex, de Bie, Rob, and Willems, Paul C.

Subjects
FOS: Clinical medicine, 110323 Surgery, 110604 Sports Medicine, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases, 110314 Orthopaedics
Abstract

Supplemental Material, sj-docx-1-gsj-10.1177_21925682211034500 for Instrumentation Techniques to Prevent Proximal Junctional Kyphosis and Proximal Junctional Failure in Adult Spinal Deformity Correction: A Systematic Review of Clinical Studies by Timon F. G. Vercoulen, Remco J. P. Doodkorte, Alex Roth, Rob de Bie and Paul C. Willems in Global Spine Journal

Published
2021
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10. Structural and functional correlates of subthalamic deep brain stimulation-induced apathy in Parkinson's disease

Author

Boon, Lennard I., Potters, Wouter V., Zoon, Thomas J. C., van den Heuvel, Odile A., Prent, Naomi, Bie, R.-O.-B. M. A. de, de Bie, Rob M. A., Bot, Maarten, Schuurman, P. Richard, van den Munckhof, Pepijn, Geurtsen, Gert J., Hillebrand, Arjan, Stam, Cornelis J., Rootselaar, Anne-Fleur van, van Rootselaar, Anne-Fleur, and Berendse, Henk W.

Subjects
nervous system
Abstract

BackgroundNotwithstanding the large improvement in motor function in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role.ObjectiveWe studied whether apathy in DBS-treated PD patients could be a stimulation effect.MethodsIn 26 PD patients we acquired apathy scores before and >6 months after DBS of the subthalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed ≥6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy.ResultsAverage apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex.ConclusionsThe present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms.

Published
2020

11. Does deep brain stimulation improve lower urinary tract symptoms in Parkinson's disease?

Author

Witte, Lambertus P., Odekerken, Vincent J. J., Boel, Judith A., Schuurman, P. Richard, Gerbrandy-Schreuders, Lara C., de Bie, Rob M. A., Schmand, Bernardus A., Geurtsen, Gert J., Movement Disorder (MD), Other departments, ANS - Neurodegeneration, Neurology, Graduate School, Neurosurgery, APH - Personalized Medicine, APH - Quality of Care, AMS - Restoration & Development, Medical Psychology, APH - Mental Health, and APH - Aging & Later Life

Subjects
Male, medicine.medical_specialty, Parkinson's disease, Deep brain stimulation, Deep Brain Stimulation, Urology, medicine.medical_treatment, 030232 urology & nephrology, Urinary incontinence, Globus Pallidus, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Lower Urinary Tract Symptoms, Subthalamic Nucleus, Lower urinary tract symptoms, Surveys and Questionnaires, medicine, Humans, Nocturia, Aged, business.industry, Parkinsonism, Parkinson Disease, Middle Aged, medicine.disease, nervous system diseases, Surgery, Subthalamic nucleus, Treatment Outcome, surgical procedures, operative, nervous system, Overactive bladder, Female, Neurology (clinical), medicine.symptom, business, therapeutics, 030217 neurology & neurosurgery
Abstract

AIMS: To investigate whether deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) or the subthalamic nucleus (STN) improve lower urinary tract symptoms (LUTS) in advanced Parkinson's disease (PD).METHODS: An exploratory post-hoc analysis was performed of specific LUTS items of questionnaires used in a randomized clinical trial with 128 patients (NSTAPS study). First, we compared scores on LUTS items at baseline and 12 months for the GPi DBS and STN DBS group separately. Second, we divided the group by sex, instead of DBS location; to assess a possible gender associated influence of anatomical and pathophysiological differences, again comparing scores at baseline and 12 months. Third, we reported on Foley-catheter use at baseline and after 12 months.RESULTS: Urinary incontinence and frequency improved after both GPi DBS and STN DBS at 12 months, postoperatively, but this was only statistically significant for the STN DBS group (P = 0.004). The improvements after DBS were present in both men (P = 0.01) and women (P = 0.05). Nocturia and urinary incontinence did not improve significantly after any type of DBS, irrespective of sex. At 12 months, none of the patients had a Foley-catheter.CONCLUSIONS: Urinary incontinence and frequency significantly improved after STN DBS treatment in male and female patients with PD. Nocturia and nighttime incontinence due to parkinsonism did not improve after DBS, irrespective of gender.

Published
2017
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12. Detecting Mild Cognitive Deficits in Parkinson's Disease: Comparison of Neuropsychological Tests

Author

Hoogland, Jeroen, van Wanrooij, Lennard L, Boel, Judith A, Goldman, Jennifer G, Stebbins, Glenn T, Dalrymple-Alford, John C, Marras, Connie, Adler, Charles H, Junque, Carme, Pedersen, Kenn F, Mollenhauer, Brit, Zabetian, Cyrus P, Eslinger, Paul J, Lewis, Simon JG, Wu, Ruey-Meei, Klein, Martin, Rodriguez-Oroz, Maria C, Cammisuli, Davide M, Barone, Paolo, Biundo, Roberta, de Bie, Rob MA, Schmand, Ben A, Tröster, Alexander I, Burn, David J, Litvan, Irene, Filoteo, J Vincent, Geurtsen, Gert J, Weintraub, Daniel, and IPMDS Study Group 'Validation of Mild Cognitive Impairment in Parkinson Disease'

Subjects
Male, cognition, Aging, Clinical Sciences, Neuropsychological Tests, Neurodegenerative, Databases, mild cognitive impairment, Clinical Research, Behavioral and Social Science, Acquired Cognitive Impairment, Humans, Cognitive Dysfunction, Bibliographic, Aged, Parkinson's Disease, Neurology & Neurosurgery, IPMDS Study Group “Validation of Mild Cognitive Impairment in Parkinson Disease”, Neurosciences, Parkinson Disease, Human Movement and Sports Sciences, Middle Aged, neuropsychological, MCI, Brain Disorders, Mental Health, Neurological, Female, Dementia
Abstract

BackgroundNumerous neuropsychological tests and test versions are used in Parkinson's disease research, but their relative capacity to detect mild cognitive deficits and their comparability across studies are unknown. The objective of this study was to identify neuropsychological tests that consistently detect cognitive decline in PD across studies.MethodsData from 30 normed neuropsychological tests across 20 international studies in up to 2908 nondemented PD patients were analyzed. A subset of 17 tests was administered to up to 1247 healthy controls. A 2-step meta-analytic approach using standardized scores compared performance in PD with normative data.ResultsPooled estimates of the differences between PD and site-specific healthy controls identified significant cognitive deficits in PD patients on 14 test scores across 5 commonly assessed cognitive domains (attention or working memory, executive, language, memory, and visuospatial abilities), but healthy control performance was statistically above average on 7 of these tests. Analyses based on published norms only, as opposed to direct assessment of healthy controls, showed high between-study variability that could not be accounted for and led to inconclusive results.ConclusionsNormed neuropsychological tests across multiple cognitive domains consistently detect cognitive deficits in PD when compared with site-specific healthy control performance, but relative PD performance was significantly affected by the inclusion and type of healthy controls versus the use of published norms only. Additional research is needed to identify a cognitive battery that can be administered in multisite international studies and that is sensitive to cognitive decline, responsive to therapeutic interventions, and superior to individual cognitive tests. © 2018 International Parkinson and Movement Disorder Society.

Published
2018

13. No genetic association between attention-deficit/hyperactivity disorder (ADHD) and Parkinson's disease in nine ADHD candidate SNPs

Author

Geissler, Julia M, Romanos, Marcel, Sheerin, Una-Marie, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Sidransky, Ellen, Smith, Colin, Spencer, Chris C A, Stefánsson, Hreinn, Steinberg, Stacy, Stockton, Joanna D, Strange, Amy, Saad, Mohamad, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J, Uitterlinden, André G, Velseboer, Daan, Vidailhet, Marie, Walker, Robert, Simón-Sánchez, Javier, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H, Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Hardy, John, Heutink, Peter, Brice, Alexis, Schulte, Claudia, Gasser, Thomas, Singleton, Andrew B, Wood, Nicholas W, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Barker, Roger, Ben-Shlomo, Yoav, Berendse, Henk W, Gerlach, Manfred, Berg, Daniela, Bhatia, Kailash, de Bie, Rob M A, Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F, Chong, Sean, Clarke, Carl E, Cookson, Mark R, Cooper, J Mark, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Deloukas, Panos, Deuschl, Günther, Dexter, David T, van Dijk, Karin D, Dillman, Allissa, Durif, Frank, Dürr, Alexandra, Edkins, Sarah, members, International Parkinson Disease Genomics Consortium, Evans, Jonathan R, Foltynie, Thomas, Gao, Jianjun, Gardner, Michelle, Gibbs, J Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Gústafsson, Ómar, Harris, Clare, Nalls, Mike, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Huber, Heiko, Hudson, Gavin, Hunt, Sarah E, Huttenlocher, Johanna, Plagnol, Vincent, Illig, Thomas, Jónsson, Pálmi V, Lambert, Jean-Charles, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Hernandez, Dena G, Moorby, Catriona, Moore, Matthew, Morris, Huw R, Morrison, Karen E, Mudanohwo, Ese, O'Sullivan, Sean S, Pearson, Justin, Perlmutter, Joel S, Pétursson, Hjörvar, Pollak, Pierre, Sharma, Manu, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Human genetics, Neurology, Amsterdam Neuroscience - Neurodegeneration, Geissler, Julia M [0000-0003-1878-9647], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Parkinson's disease, Single-nucleotide polymorphism, Genome-wide association study, genetics [Attention Deficit Disorder with Hyperactivity], Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, genetics [Parkinson Disease], medicine, Attention deficit hyperactivity disorder, ADHD, GWAS, Humans, Genetic Predisposition to Disease, ddc:610, genetics [Genetic Predisposition to Disease], Genetic Association Studies, Genetic association, Dopamine transporter, Genetics, TPH2, biology, Parkinson Disease, General Medicine, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], medicine.disease, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Norepinephrine transporter, Attention Deficit Disorder with Hyperactivity, biology.protein, genetics [Polymorphism, Single Nucleotide], Parkinson’s disease, Psychology, 030217 neurology & neurosurgery, CDH13, SNPs
Abstract

Item does not contain fulltext Attention-deficit/hyperactivity disorder (ADHD) and Parkinson's disease (PD) involve pathological changes in brain structures such as the basal ganglia, which are essential for the control of motor and cognitive behavior and impulsivity. The cause of ADHD and PD remains unknown, but there is increasing evidence that both seem to result from a complicated interplay of genetic and environmental factors affecting numerous cellular processes and brain regions. To explore the possibility of common genetic pathways within the respective pathophysiologies, nine ADHD candidate single nucleotide polymorphisms (SNPs) in seven genes were tested for association with PD in 5333 cases and 12,019 healthy controls: one variant, respectively, in the genes coding for synaptosomal-associated protein 25 k (SNAP25), the dopamine (DA) transporter (SLC6A3; DAT1), DA receptor D4 (DRD4), serotonin receptor 1B (HTR1B), tryptophan hydroxylase 2 (TPH2), the norepinephrine transporter SLC6A2 and three SNPs in cadherin 13 (CDH13). Information was extracted from a recent meta-analysis of five genome-wide association studies, in which 7,689,524 SNPs in European samples were successfully imputed. No significant association was observed after correction for multiple testing. Therefore, it is reasonable to conclude that candidate variants implicated in the pathogenesis of ADHD do not play a substantial role in PD.

Published
2018
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14. Detecting Mild Cognitive Deficits in Parkinson's Disease: Comparison of Neuropsychological Tests

Author

Hoogland, Jeroen, van Wanrooij, Lennard L., Boel, Judith A., Goldman, Jennifer G., Stebbins, Glenn T., Dalrymple-Alford, John C., Marras, Connie, Adler, Charles H., Junque, Carme, Pedersen, Kenn F., Mollenhauer, Brit, Zabetian, Cyrus P., Eslinger, Paul J., Lewis, Simon J.G., Wu, Ruey Meei, Klein, Martin, Rodriguez-Oroz, Maria C., Cammisuli, Davide M., Barone, Paolo, Biundo, Roberta, de Bie, Rob M.A., Schmand, Ben A., Tröster, Alexander I., Burn, David J., Litvan, Irene, Filoteo, J. Vincent, Geurtsen, Gert J., Weintraub, Daniel, VU University medical center, Medical psychology, NCA - Neurobiology of mental health, Amsterdam Neuroscience - Neurodegeneration, Psychology Other Research (FMG), and FMG

Subjects
Male, Humans, Cognitive Dysfunction, Female, Parkinson Disease, Middle Aged, Neuropsychological Tests, Databases, Bibliographic, Article, Aged
Abstract

Background: Numerous neuropsychological tests and test versions are used in Parkinson's disease research, but their relative capacity to detect mild cognitive deficits and their comparability across studies are unknown. The objective of this study was to identify neuropsychological tests that consistently detect cognitive decline in PD across studies. Methods: Data from 30 normed neuropsychological tests across 20 international studies in up to 2908 nondemented PD patients were analyzed. A subset of 17 tests was administered to up to 1247 healthy controls. A 2‐step meta‐analytic approach using standardized scores compared performance in PD with normative data. Results : Pooled estimates of the differences between PD and site‐specific healthy controls identified significant cognitive deficits in PD patients on 14 test scores across 5 commonly assessed cognitive domains (attention or working memory, executive, language, memory, and visuospatial abilities), but healthy control performance was statistically above average on 7 of these tests. Analyses based on published norms only, as opposed to direct assessment of healthy controls, showed high between‐study variability that could not be accounted for and led to inconclusive results. Conclusions: Normed neuropsychological tests across multiple cognitive domains consistently detect cognitive deficits in PD when compared with site‐specific healthy control performance, but relative PD performance was significantly affected by the inclusion and type of healthy controls versus the use of published norms only. Additional research is needed to identify a cognitive battery that can be administered in multisite international studies and that is sensitive to cognitive decline, responsive to therapeutic interventions, and superior to individual cognitive tests. © 2018 International Parkinson and Movement Disorder Society

Published
2018
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15. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Author

Consortium, Coffee and Caffeine Genetics, Cornelis, Marilyn C, Renstrom, Frida, Rasheed, Asif, Mason, Marc A, Zonderman, Alan B, Franke, Lude, Kristal, Bruce S, Consortium, International Parkinson’s Disease Genomics, Consortium, North American Brain Expression, Consortium, UK Brain Expression, Karjalainen, Juha, Reed, Danielle R, Ngwa, Julius S, Westra, Harm-Jan, Evans, Michele K, Saleheen, Danish, Harris, Tamara B, Dedoussis, George, Curhan, Gary, Stumvoll, Michael, Beilby, John, Pasquale, Louis R, Feenstra, Bjarke, Huikari, Ville, Bandinelli, Stefania, Ordovas, Jose M, Chan, Andrew T, Peters, Ulrike, Ohlsson, Claes, Gieger, Christian, Martin, Nicholas G, Waldenberger, Melanie, Siscovick, David S, Raitakari, Olli, Cavadino, Alana, Eriksson, Johan G, Mitchell, Paul, Hunter, David J, Kraft, Peter, Rimm, Eric B, Boomsma, Dorret I, Borecki, Ingrid B, Loos, Ruth Jf, Wareham, Nicholas J, Vollenweider, Peter, Nolte, Ilja M, Caporaso, Neil, Grabe, Hans Jörgen, Neuhouser, Marian L, Wolffenbuttel, Bruce Hr, Hu, Frank B, Hyppönen, Elina, Järvelin, Marjo-Riitta, Cupples, L Adrienne, Franks, Paul W, Ridker, Paul M, Teumer, Alexander, van Duijn, Cornelia M, Heiss, Gerardo, Metspalu, Andres, North, Kari E, Ingelsson, Erik, Nettleton, Jennifer A, van Dam, Rob M, Chasman, Daniel I, Nalls, Michael A, Plagnol, Vincent, Yu, Kai, Hernandez, Dena G, Sharma, Manu, Sheerin, Una-Marie, Saad, Mohamad, Simón-Sánchez, Javier, Schulte, Claudia, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Barker, Roger, Marques-Vidal, Pedro, Ben-Shlomo, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob M A, Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, M., Rawal, Rajesh, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F, Chong, Sean, Clarke, Carl E, Cookson, Mark R, Cooper, J Mark, Manichaikul, Ani, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Deloukas, Panos, Deuschl, Günther, Dexter, David T, van Dijk, Karin D, Dillman, Allissa, Durif, Frank, Byrne, Enda M, Wojczynski, Mary K, Dürr, Alexandra, Edkins, Sarah, Evans, Jonathan R, Foltynie, Thomas, Dong, Jing, Gardner, Michelle, Gibbs, J Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Vink, Jacqueline M, Harris, Clare, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Hershey, Milton S, Wurster, Isabel, Mätzler, Walter, Zhao, Jing Hua, Hudson, Gavin, Hunt, Sarah E, Huttenlocher, Johanna, Illig, Thomas, München, Helmholtz Zentrum, Jónsson, Pálmi V, Lambert, Jean-Charles, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Burlutsky, George, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw R, Morrison, Karen E, O' Sullivan, Sean S, Lahti, Jari, Pearson, Justin, Perlmutter, Joel S, Pétursson, Hjörvar, Pollak, Pierre, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Mikkilä, Vera, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Sidransky, Ellen, Smith, Colin, Spencer, Chris C A, Stefánsson, Hreinn, Bettella, Francesco, Lemaitre, Rozenn N, Stockton, Joanna D, Strange, Amy, Talbot, Kevin, Tanner, M., Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J, Uitterlinden, André G, Velseboer, Daan, Eriksson, Joel, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H, Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Sabatier, Paul, Musani, Solomon K, Wood, Nicholas W, Hardy, John, Heutink, Peter, Brice, Alexis, Gasser, Thomas, Singleton, Andrew B, Singleton, Andrew, Cookson, Mark, Hernandez, Dena, Tanaka, Toshiko, Nalls, Michael, Zonderman, Alan, Ferrucci, Luigi, Johnson, Robert, Longo, Dan, O'Brien, Richard, Traynor, Bryan, Troncoso, Juan, Esko, Tõnu, Geller, Frank, van der Brug, Marcel, Zielke, Ronald, Weale, Michael, Ramasamy, Adaikalavan, Box, P. O., Luan, Jian'an, Hui, Jennie, Mägi, Reedik, Dimitriou, Maria, Garcia, Melissa E, Ho, Weang-Kee, Wright, Margaret J, Rose, Lynda M, Magnusson, Patrik Ke, Pedersen, Nancy L, Couper, David, Oostra, Ben A, Ikram, Mohammad Arfan, Tiemeier, Henning W, Uitterlinden, Andre G, van Rooij, Frank Ja, Barroso, Inês, Johansson, Ingegerd, Ganna, Andrea, Xue, Luting, Kaakinen, Marika, Milani, Lili, Power, Chris, Snieder, Harold, Stolk, Ronald P, Baumeister, Sebastian E, Biffar, Reiner, Gu, Fangyi, Bastardot, François, Paynter, Nina, Kutalik, Zoltán, Jacobs, David R, Forouhi, Nita G, Mihailov, Evelin, Lind, Lars, Lindgren, Cecilia, Michaëlsson, Karl, Morris, Andrew, Jensen, Majken, Khaw, Kay-Tee, Monda, Keri L, Luben, Robert N, Wang, Jie Jin, Männistö, Satu, Perälä, Mia-Maria, Kähönen, Mika, Lehtimäki, Terho, Viikari, Jorma, Mozaffarian, Dariush, Mukamal, Kenneth, Psaty, Bruce M, Amin, Najaf, Döring, Angela, Heath, Andrew C, Montgomery, Grant W, Dahmen, Norbert, Carithers, Teresa, Tucker, Katherine L, Boyd, Heather A, Melbye, Mads, Treur, Jorien L, Fischer, Krista, Mellström, Dan, Hottenga, Jouke Jan, Prokopenko, Inga, Tönjes, Anke, Kanoni, Stavroula, Lorentzon, Mattias, Houston, Denise K, Liu, Yongmei, Danesh, John, Biological Psychology, Nutrition and Health, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, The, Coffee, Cornelis, MC, Byrne, Enda, Esko, Tonu, Nalls, MA, Hyppönen, Elina, Chasman, DI, The Coffee and Caffeine Genetics Consortium, International Parkinson's Disease Genomics Consortium (IPDGC), UK Brain Expression Consortium (UKBEC), North American Brain Expression Consortium (NABEC), Epidemiology, Surgery, Public Health, Cell biology, Hematology, Clinical Genetics, Internal Medicine, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), ANS - Amsterdam Neuroscience, Neurology, Graduate School, Pediatric surgery, VU University medical center, NCA - neurodegeneration, Human genetics, NCA - Brain mechanisms in health and disease, and NCA - Neurobiology of mental health

Subjects
INVOLVEMENT, Netherlands Twin Register (NTR), GCKR protein, human, PROTEIN, Genome-wide association study, VARIANTS, genetics [Brain-Derived Neurotrophic Factor], chemistry.chemical_compound, 0302 clinical medicine, Polymorphism (computer science), genetics [Adaptor Proteins, Signal Transducing], BINDING, BRAIN, Genetics, 0303 health sciences, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Psychiatry and Mental health, Phenotype, genetics [Polymorphism, Single Nucleotide], genetics [Cytochrome P-450 CYP1A2], Caffeine, CAFFEINE, Single-nucleotide polymorphism, Biology, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Cytochrome P-450 CYP1A2, SNP, Humans, ddc:610, Allele, genetics [Basic Helix-Loop-Helix Leucine Zipper Transcription Factors], Molecular Biology, 030304 developmental biology, Adaptor Proteins, Signal Transducing, MLXIPL protein, human, RECEPTOR, Brain-Derived Neurotrophic Factor, Coffea, ta1182, Feeding Behavior, biology.organism_classification, ta3124, BDNF, chemistry, Behavioral medicine, Developmental Psychopathology, 030217 neurology & neurosurgery, GLUCOKINASE, metabolism [Coffea], Genome-Wide Association Study
Abstract

Contains fulltext : 155360.pdf (Publisher’s version ) (Closed access) Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P

Published
2015
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16. Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing

Author

Jansen, Iris E, Ye, Hui, Gibbs, J Raphael, Illig, Thomas, Jónsson, Pálmi V, Lambert, Jean-Charles, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, Lungu, Codrin, Nalls, Mike A, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw R, Morrison, Karen E, Escott-Price, Valentina, Mudanohwo, Ese, O'Sullivan, Sean S, Pearson, Justin, Perlmutter, Joel S, Ryten, Mina, Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Sawcer, Stephen, Botia, Juan A, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Shulman, Joshua, Sidransky, Ellen, Smith, Colin, Spencer, Chris C A, Stefánsson, Hreinn, Bettella, Francesco, Vandrovcova, Jana, Stockton, Joanna D, Strange, Amy, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J, Uitterlinden, André G, Velseboer, Daan, Simon Sanchez, Javier, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H, Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Wood, Nicholas W, Castillo Lizardo, Melissa Gissel, Hardy, John, Heutink, Peter, Brice, Alexis, Gasser, Thomas, Singleton, Andrew B, Rizzu, Patrizia, Blauwendraat, Cornelis, Chouhan, Amit K, Heetveld, Sasja, Li, Yarong, Yogi, Puja, Amin, Najaf, van Duijn, Cornelia M, Consortium, International Parkinson’s Disease Genetics, David, Della C, Nollen, Ellen A, Lechler, Marie C, Jain, Shushant, Shulman, Joshua M, Plagnol, Vincent, Hernandez, Dena G, Sharma, Manu, Sheerin, Una-Marie, Saad, Mohamad, SimónSánchez, Javier, Schulte, Claudia, Michels, Helen, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Barker, Roger, Ben-Shlomo, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob M A, Biffi, Alessandro, Seinstra, Renée I, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Majounie, Elisa, Lubbe, Steven, Price, Ryan, Lubbe, Steven J, Nicolas, Aude, Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F, Chong, Sean, Clarke, Carl E, Cookson, Mark R, Cooper, J Mark, Corvol, Jean Christophe, Drouet, Valérie, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Deloukas, Panos, Deuschl, Günther, Dexter, David T, van Dijk, Karin D, Dillman, Allissa, Durif, Frank, Dürr, Alexandra, Edkins, Sarah, Evans, Jonathan R, Foltynie, Thomas, Dong, Jing, Gardner, Michelle, Goate, Alison, Gray, Emma, Guerreiro, Rita, Harris, Clare, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Wurster, Isabel, Mätzler, Walter, Hudson, Gavin, Hunt, Sarah E, Huttenlocher, Johanna, Epidemiology, Neurology, Amsterdam Neuroscience - Neurodegeneration, Human genetics, ANS - Neurodegeneration, Graduate School, ANS - Neuroinfection & -inflammation, Botia, Juan A [0000-0002-6992-598X], Chouhan, Amit K [0000-0003-2991-6402], Amin, Najaf [0000-0002-8944-1771], van Duijn, Cornelia M [0000-0002-2374-9204], David, Della C [0000-0001-8597-9470], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Candidate gene, G-PATCH, Parkinson's disease, methods [Sequence Analysis, DNA], Compound heterozygosity, AXON GUIDANCE, Animals, Genetically Modified, DOMAIN-CONTAINING 2, genetics [Parkinson Disease], Exome, Child, Cells, Cultured, Exome sequencing, Genetics, genetics [Drosophila melanogaster], High-Throughput Nucleotide Sequencing, Parkinson Disease, Genomics, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Mitochondria, ALZHEIMERS-DISEASE, Drosophila melanogaster, Whole-exome sequencing, genetics [alpha-Synuclein], alpha-Synuclein, genetics [Caenorhabditis elegans], RNA Interference, Adult, methods [High-Throughput Nucleotide Sequencing], NETWORK ANALYSIS, Adolescent, Biology, Loss-of-function, Young Adult, 03 medical and health sciences, α-synuclein, SDG 3 - Good Health and Well-being, ddc:570, Functional screening, Animals, Humans, Animal model, Genetic Predisposition to Disease, Allele, Caenorhabditis elegans, Parkin, RECEPTOR TYROSINE PHOSPHATASE, Research, RETROMER COMPLEX, Rare variants, Sequence Analysis, DNA, Human genetics, Retromer complex, DROSOPHILA MODEL, Disease Models, Animal, 030104 developmental biology, Case-Control Studies, Parkinson’s disease, CAENORHABDITIS-ELEGANS
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. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1147-9) contains supplementary material, which is available to authorized users.

Published
2017
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17. The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism

Author

Klebe, Stephan, Golmard, Jean-Louis, Charfi, Rim, Edkins, Sarah, Evans, Jonathan R, Foltynie, Thomas, Freeman, Colin, Gao, Jianjun, Gardner, Michelle, Gibbs, Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Klein, Christine, Gústafsson, Omar, Harris, Clare, Hellenthal, Garrett, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Huber, Heiko, Hagenah, Johann, Hudson, Gavin, Hunt, Sarah E, Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Gasser, Thomas, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Morris, Huw, Morrison, Karen E, Mudanohwo, Ese, O'Sullivan, Sean S, Pearson, Justin, Pearson, Richard, Perlmutter, Joel S, Wurster, Isabel, Pétursson, Hjörvar, Pirinen, Matti, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Lesage, Suzanne, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Sidransky, Ellen, de Silva, Rohan, Smith, Colin, Spencer, Chris Ca, Stefánsson, Hreinn, Steinberg, Stacy, Stockton, Joanna D, Strange, Amy, Su, Zhan, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Deuschl, Günther, Traynor, Bryan J, Uitterlinden, G., Vandrovcova, Jana, Velseboer, Daan, Vidailhet, Marie, Vukcevic, Damjan, Walker, Robert, van de Warrenburg, Bart, Weale, Michael E, Wickremaratchi, Mirdhu, Durif, Franck, Williams, Nigel, Williams-Gray, Caroline H, Winder-Rhodes, Sophie, Martinez, Maria, Donnelly, Peter, Hardy, John, Heutink, Peter, Brice, Alexis, Wood, Nicholas W, Singleton, Andrew B, Nalls, Michael A, Damier, Philippe, Durr, Alexandra, Amouyel, Philippe, Lambert, Jean-Charles, Tzourio, Christophe, Maubaret, Cécilia, Charbonnier-Beaupel, Fanny, Tahiri, Khadija, Saad, Mohamad, Corvol, Jean-Christophe, Group, French Parkinson's Disease Genetics Study, Consortium, International Parkinson's Disease Genomics, Agid, Y., Anheim, M., Bonnet, A-M, Borg, M., Brice, A., Broussolle, E., Corvol, J-C, Damier, Ph, Destée, A., Durr, A., Durif, F., Klebe, S., Lohmann, E., Martinez, M., Penet, C., Bras, Jose M, Pollak, P., Krack, P., Rascol, O., Tison, F., Tranchant, C., Vérin, M., Viallet, F., Plagnol, Vincent, Hernandez, Dena G, Sharma, Manu, Sheerin, Una-Marie, Simón-Sánchez, Javier, Schulte, Claudia, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Band, Gavin, Simon-Sanchez, Javier, Barker, Roger A, Bellinguez, Céline, Ben-Shlomo, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob Ma, Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F, Chong, Sean, Clarke, Carl E, Cookson, Mark R, Kuhlenbäumer, Gregor, Cooper, J Mark, Corvol, Jean Christophe, Counsell, Carl, Dartigues, Jean-François, Deloukas, Panos, Dexter, David T, van Dijk, Karin D, Dillman, Allissa, Durif, Frank, INSERM UMR_S9745, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Biostatistiques [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UCL Institute of neurology, UCL Institute of Neurology, Department of Clinical Genetics, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institute of Experimental Medicine, Christian-Albrechts-University, Department of Neurology, University of Lübeck, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Christian-Albrechts-Universität zu Kiel (CAU), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de neurologie [Univ. Paris VII], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departamento de Geologia CICESE, Centro de Investigacion Cientifica y de Education Superior de Ensenada [Mexico] (CICESE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Human genetics, NCA - Brain mechanisms in health and disease, NCA - neurodegeneration, Child and Adolescent Psychiatry / Psychology, ANS - Amsterdam Neuroscience, Neurology, Graduate School, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Département de Neurologie [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP]

Subjects
Male, medicine.medical_specialty, Genotype, DCN MP - Plasticity and memory, [SDV]Life Sciences [q-bio], genetics [Catechol O-Methyltransferase], Neurogenetics, Catechol O-Methyltransferase/genetics, Catechol O-Methyltransferase, Polymorphism, Single Nucleotide, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], 03 medical and health sciences, Sex Factors, 0302 clinical medicine, genetics [Parkinson Disease], Internal medicine, medicine, Humans, ddc:610, Parkinson Disease/genetics, Age of Onset, Allele, Aged, 030304 developmental biology, Genetics, 0303 health sciences, Movement Disorders, Parkinson's Disease, Catechol-O-methyl transferase, Parkinson Disease, Middle Aged, Polymorphism, Single Nucleotide/genetics, ddc:616.8, Sexual dimorphism, Psychiatry and Mental health, Human Movement & Fatigue [DCN MP - Plasticity and memory NCEBP 10], Endocrinology, Cohort, genetics [Polymorphism, Single Nucleotide], Surgery, Neurology (clinical), Age of onset, Psychology, 030217 neurology & neurosurgery, rs4680
Abstract

Item does not contain fulltext The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD). The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1+/-13.9, p=0.03) than the Val/Met (57.4+/-13.9) and the Met/Met genotypes (58.3+/-13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD.

Published
2013
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18. Arthroplasty versus fusion for single-level cervical degenerative disc disease

Author

Willems, Paul C, van Mameren, Henk, de Bie, Rob, van Santbrink, Henk, and Boselie, Toon FM

Subjects
Medicine General & Introductory Medical Sciences, 03 medical and health sciences, 0302 clinical medicine, Pharmacology (medical), 030212 general & internal medicine, 030217 neurology & neurosurgery
Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows: The goal of this updated systematic review is to determine whether discectomy with fusion or discectomy with arthroplasty provides the best clinical, functional, and radiological outcomes, with the least adverse effects, for patients with symptomatic single level cervical degenerative disc disease.

Published
2016
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19. Genetic comorbidities in Parkinson's disease

Author

Nalls, Mike A, Saad, Mohamad, Morris, Huw R, Mudanohwo, Ese, O'Sullivan, Sean S, Pearson, Justin, Perlmutter, Joel S, Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Williams, Nigel, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Sidransky, Ellen, Gasser, Thomas, Smith, Colin, Spencer, Chris C A, Stefánsson, Hreinn, Steinberg, Stacy, Stockton, Joanna D, Strange, Amy, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Heutink, Peter, Trabzuni, Daniah, Traynor, Bryan J, Uitterlinden, André G, Velseboer, Daan, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams-Gray, Caroline H, Wood, Nick, Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Hardy, John, Brice, Alexis, Singleton, Andrew B, Wood, Nicholas W, Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, N. A., Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Su, Zhan, Vukcevic, Damjan, Consortium, International Parkinson's Disease Genomics, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, 2, Wellcome Trust Case Control Consortium, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Noyce, Alastair J, Consortium, North American Brain Expression, McCarthy, Mark I, Cookson, Mark R, Consortium, United Kingdom Brain Expression, Gibbs, J Raphael, Hernandez, Dena G, Dillman, Allissa, Nalls, Michael A, Zonderman, Alan B, Arepalli, Sampath, Ferrucci, Luigi, Johnson, Robert, Longo, Dan L, O'Brien, Richard, Nalls, Mike, Traynor, Bryan, Troncoso, Juan, van der Brug, Marcel, Zielke, Ronald H, Weale, Michael E, Ramasamy, Adaikalavan, Plagnol, Vincent, Walker, Rober, Sharma, Manu, Sheerin, Una-Marie, Simón-Sánchez, Javier, Schulte, Claudia, Keller, Margaux F, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Barker, Roger, Ben-Shlomo, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob M A, Biffi, Alessandro, Schrag, Anette, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F, Bestwick, Jonathan P, Chong, Sean, Clarke, Carl E, Cooper, J Mark, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Deuschl, Günther, Dexter, David T, van Dijk, Karin D, Durif, Frank, Dürr, Alexandra, Evans, Jonathan R, Foltynie, Thomas, Gao, Jianjun, Gardner, Michelle, Goate, Alison, Guerreiro, Rita, Gústafsson, Ómar, Harris, Clare, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Huber, Heiko, Hudson, Gavin, Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V, Lambert, Jean-Charles, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morrison, Karen E, ANS - Amsterdam Neuroscience, Neurology, Graduate School, and Erasmus MC other

Subjects
genetics [Crohn Disease], epidemiology [Schizophrenia], Single-nucleotide polymorphism, Genome-wide association study, Disease, Comorbidity, Biology, Bioinformatics, Inflammatory bowel disease, Polymorphism, Single Nucleotide, Crohn Disease, genetics [Parkinson Disease], Risk Factors, ddc:570, Mendelian randomization, mental disorders, Genetics, medicine, Humans, Genetic Predisposition to Disease, genetics [Schizophrenia], Molecular Biology, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Genetics (clinical), Genetic association, epidemiology [Crohn Disease], Association Studies Articles, Parkinson Disease, General Medicine, DNA Methylation, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Schizophrenia, CpG Islands, epidemiology [Parkinson Disease], Genome-Wide Association Study
Abstract

Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain.

Published
2014
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20. Analysis of Genome-Wide Association Studies of Alzheimer Disease and of Parkinson Disease to Determine If These 2 Diseases Share a Common Genetic Risk

Author

Moskvina, Valentina, Harold, Denise, Nicolaou, Nayia, Simón-Sánchez, Javier, Gibbs, J Raphael, Schulte, Claudia, Durr, Alexandra, Guerreiro, Rita, Hernandez, Dena, Brice, Alexis, Stefánsson, Hreinn, Majamaa, Kari, Russo, GianCarlo, Gasser, Thomas, Heutink, Peter, Wood, Nick, Martinez, Maria, Singleton, Andrew B, Nalls, Michael A, Hardy, John, Owen, Michael J, O'Donovan, Michael C, Williams, Julie, Vedernikov, Alexey, Morris, Huw R, Williams, Nigel M, Investigators, IPDGC and GERAD, Dillman, Allissa, Brooks, Janet, Chong, Sean, Cookson, Mark R, Moore, Matthew, Keller, Margaux F, Sharma, Manu, Traynor, Bryan J, Arepalli, Sampath, Charlesworth, Gavin, Plagnol, Vincent, Ryten, Mina, Trabzuni, Daniah, Bras, Jose M, Saad, Mohamed, Sheerin, Una-Marie, Bhatia, Kailash, Saad, Mohamad, Bochdanovits, Zoltan, Rizzu, Patrizia, Vidailhet, Marie, Holmans, Peter, Corvol, Jen-Christophe, Curie, Pierre et Marie, Barker, Roger, Hunt, Sarah E, Gray, Emma, Edkins, Sarah, Tashakkori-Ghanbaria, Avazeh, Barrett, Jeffrey, Deloukasm, Panagiotis, Potter, Simon, Ben-Shlomo, Yoav, van Dijk, Karin D, Berendse, Henk W, Velseboer, Daan, de Bie, Rob M A, Biffi, Alessandro, Bloem, Bas, van deWarrenburg, Bart, Post, Bart, Bettella, Francesco, Riess, Olaf, Bonin, Michael, Burn, David J, Human genetics, NCA - neurodegeneration, Graduate School, ANS - Amsterdam Neuroscience, and Neurology

Subjects
Adult, Male, statistics & numerical data [Databases, Factual], Databases, Factual, Genotype, genetics [Alzheimer Disease], Single-nucleotide polymorphism, Genome-wide association study, Disease, In Vitro Techniques, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Article, Gene Frequency, genetics [Parkinson Disease], Alzheimer Disease, Risk Factors, medicine, Humans, Dementia, Genetic Predisposition to Disease, ddc:610, genetics [Genetic Predisposition to Disease], Allele, Allele frequency, Aged, Genetic association, Aged, 80 and over, Genetics, Parkinson Disease, Middle Aged, medicine.disease, United States, Europe, Meta-analysis, genetics [Polymorphism, Single Nucleotide], Female, Neurology (clinical), Genome-Wide Association Study
Abstract

Importance Despite Alzheimer disease (AD) and Parkinson disease (PD) being clinically distinct entities, there is a possibility of a pathological overlap, with some genome-wide association (GWA) studies suggesting that the 2 diseases represent a biological continuum. The application of GWA studies to idiopathic forms of AD and PD have identified a number of loci that contain genetic variants that increase the risk of these disorders. Objective To assess the genetic overlap between PD and AD by testing for the presence of potentially pleiotropic loci in 2 recent GWA studies of PD and AD. Design Combined GWA analysis. Setting Data sets from the United Kingdom, Germany, France, and the United States. Participants Thousands of patients with AD or PD and their controls. Main Outcomes and Measures Meta-analysis of GWA studies of AD and PD. Methods To identify evidence for potentially pleiotropic alleles that increased the risk for both PD and AD, we performed a combined PD-AD meta-analysis and compared the results with those obtained in the primary GWA studies. We also tested for a net effect of potentially polygenic alleles that were shared by both disorders by performing a polygenic score analysis. Finally, we also performed a gene-based association analysis that was aimed at detecting genes that harbor multiple disease-causing single-nucleotide polymorphisms, some of which confer a risk of PD and some a risk of AD. Results Detailed interrogation of the single-nucleotide polymorphism, polygenic, and gene-based analyses resulted in no significant evidence that supported the presence of loci that increase the risk of both PD and AD. Conclusions and Relevance Our findings therefore imply that loci that increase the risk of both PD and AD are not widespread and that the pathological overlap could instead be “downstream” of the primary susceptibility genes that increase the risk of each disease.

Published
2013
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21. Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review

Author

Volkmann, Jens, Albanese, Alberto, Antonini, Angelo, Chaudhuri, K Ray, Clarke, Carl E, de Bie, Rob M A, Deuschl, Günther, Eggert, Karla, Houeto, Jean-Luc, Kulisevsky, Jaime, Nyholm, Dag, Odin, Per, Østergaard, Karen, Poewe, Werner, Pollak, Pierre, Rabey, Jose Martin, Rascol, Olivier, Ruzicka, Evzen, Samuel, Michael, Speelman, Hans, Sydow, Olof, Valldeoriola, Francesc, van der Linden, Chris, and Oertel, Wolfgang

Subjects
Duodenal levodopa infusion, Apomorphine, Parkinson's disease, Deep brain stimulation, ddc:616.8
Abstract

Motor complications in Parkinson's disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Published
2013

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

Author

Keller, Margaux F, Saad, Mohamad, Schulte, Claudia, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw R, Morrison, Karen E, Mudanohwo, Ese, O'Sullivan, Sean S, Moskvina, Valentina, Pearson, Justin, Perlmutter, Joel S, Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Durr, Alexandra, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Sidransky, Ellen, Smith, Colin, Spencer, Chris C A, Holmans, Peter, Stefánsson, Hreinn, Steinberg, Stacy, Stockton, Joanna D, Strange, Amy, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J, Kilarski, Laura L, Uitterlinden, André G, Velseboer, Daan, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H, Winder-Rhodes, Sophie, Stefánsson, Kári, Guerreiro, Rita, Martinez, Maria, Sabatier, Paul, Hardy, John, Brice, Alexis, Singleton, Andrew B, Wood, Nicholas W, Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Hernandez, Dena G, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Ylikotila, Pauli, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Bras, Jose, Majamaa, Kari, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Gasser, Thomas, Heutink, Peter, Nalls, Michael A, Bettella, Francesco, Consortium, International Parkinson's Disease Genomics, 2, Wellcome Trust Case Control Consortium, Plagnol, Vincent, Sheerin, Una-Marie, Simón-Sánchez, Javier, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Nicolaou, Nayia, Arepalli, Sampath, Ben-Shlomo, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob M A, Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F, Chong, Sean, Clarke, Carl E, Cookson, Mark R, Mittag, Florian, Cooper, J Mark, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Segalen, Victor, Deuschl, Günther, Dexter, David T, van Dijk, Karin D, Büchel, Finja, Dillman, Allissa, Durif, Frank, Montpied, Gabriel, Evans, Jonathan R, Foltynie, Thomas, Gao, Jianjun, Gardner, Michelle, Gibbs, J Raphael, Goate, Alison, Sharma, Manu, Gústafsson, Omar, Harris, Clare, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Huber, Heiko, Hudson, Gavin, Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V, Lambert, Jean-Charles, Lees, Andrew, Lichtner, Peter, ANS - Amsterdam Neuroscience, Neurology, ACS - Amsterdam Cardiovascular Sciences, Graduate School, Human genetics, and NCA - Neurodegeneration

Subjects
Adult, Male, medicine.medical_specialty, Multifactorial Inheritance, Parkinson's disease, Functional Neurogenomics Human Movement & Fatigue [DCN 2], Single-nucleotide polymorphism, Genome-wide association study, Quantitative trait locus, Biology, Genome, White People, 03 medical and health sciences, Quantitative Trait, Heritable, 0302 clinical medicine, genetics [Parkinson Disease], Missing heritability problem, Molecular genetics, ddc:570, medicine, Genetics, Humans, Genetic Predisposition to Disease, Molecular Biology, Genetics (clinical), Aged, 030304 developmental biology, Genetic association, Aged, 80 and over, 0303 health sciences, Association Studies Articles, Genetic Variation, Family aggregation, Parkinson Disease, General Medicine, Middle Aged, Heritability, medicine.disease, Corrigenda, 3. Good health, genetics [European Continental Ancestry Group], Human Movement & Fatigue [DCN MP - Plasticity and memory NCEBP 10], Female, Trait analysis, 030217 neurology & neurosurgery, Imputation (genetics), Genome-Wide Association Study
Abstract

Contains fulltext : 110130.pdf (Publisher’s version ) (Closed access) 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
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