Search

Your search keyword '"Wszolek, ZK"' showing total 744 results
Start Over Author "Wszolek, ZK"
744 results on '"Wszolek, ZK"'

1. Cognitive profile of LRRK2-related Parkinson's disease

Author

Srivatsal, S, Cholerton, B, Leverenz, JB, Wszolek, ZK, Uitti, RJ, Dickson, DW, Weintraub, D, Trojanowski, JQ, Van Deerlin, VM, Quinn, JF, Chung, KA, Peterson, AL, Factor, SA, Wood-Siverio, C, Goldman, JG, Stebbins, GT, Bernard, B, Ritz, B, Rausch, R, Espay, AJ, Revilla, FJ, Devoto, J, Rosenthal, LS, Dawson, TM, Albert, MS, Mata, IF, Hu, SC, Montine, KS, Johnson, C, Montine, TJ, Edwards, KL, Zhang, J, and Zabetian, CP

Subjects
Neurology & Neurosurgery, Clinical Sciences, Human Movement and Sports Sciences, Cognitive Sciences, Neurosciences
Abstract

Background: Increasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2 gene are the most common cause of monogenic PD; however, the cognitive profile of LRRK2-related PD is not well-characterized. Methods: A cohort of 1,447 PD patients enrolled in the PD Cognitive Genetics Consortium was screened for LRRK2 mutations and completed detailed cognitive testing. Associations between mutation carrier status and cognitive test scores were assessed using linear regression models. Results: LRRK2 mutation carriers (n=29) demonstrated better performance on the Mini Mental State Examination (P=0.03) and the Letter-Number Sequencing Test (P=0.005). A smaller proportion of LRRK2 carriers were demented (P=0.03). Conclusions: Our cross-sectional study demonstrates better performance on certain cognitive tests, as well as lower rates of dementia in LRRK2-related PD. Future longitudinal studies are needed to determine whether LRRK2 mutation carriers exhibit slower cognitive decline.

Published
2015

2. Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease)

Author

Oliveira, JRM, Spiteri, E, Sobrido, MJ, Hopfer, S, Klepper, J, Voit, T, Gilbert, J, Wszolek, ZK, Calne, DB, Stoessl, AJ, Hutton, M, Manyam, BV, Boller, F, Baquero, M, and Geschwind, DH

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Rare Diseases, Neurodegenerative, Genetics, Neurological, Basal Ganglia Diseases, Calcinosis, Chromosomes, Human, Pair 14, Female, Genes, Dominant, Genetic Heterogeneity, Humans, Lod Score, Male, Neurologic Examination, Pedigree, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

Familial idiopathic basal ganglia calcification (IBGC, Fahr disease) is an inherited neurologic condition characterized by basal ganglia and extra-basal ganglia brain calcifications, parkinsonism, and neuropsychiatric symptoms. The authors examined six families for linkage to the previously identified genetic locus (IBGC1) located on chromosome 14q. The authors found evidence against linkage to IBGC1 in five of the six families supporting previous preliminary studies demonstrating genetic heterogeneity in familial IBGC.

Published
2004

4. Common Variants Near ZIC1 and ZIC4 in Autopsy-Confirmed Multiple System Atrophy.

Author

Hopfner, F, Tietz, AK, Ruf, VC, Ross, OA, Koga, S, Dickson, D, Aguzzi, A, Attems, J, Beach, T, Beller, A, Cheshire, WP, van Deerlin, V, Desplats, P, Deuschl, G, Duyckaerts, C, Ellinghaus, D, Evsyukov, V, Flanagan, ME, Franke, A, Frosch, MP, Gearing, M, Gelpi, E, van Gerpen, JA, Ghetti, B, Glass, JD, Grinberg, LT, Halliday, G, Helbig, I, Höllerhage, M, Huitinga, I, Irwin, DJ, Keene, DC, Kovacs, GG, Lee, EB, Levin, J, Martí, MJ, Mackenzie, I, McKeith, I, Mclean, C, Mollenhauer, B, Neumann, M, Newell, KL, Pantelyat, A, Pendziwiat, M, Peters, A, Molina Porcel, L, Rabano, A, Matěj, R, Rajput, A, Reimann, R, Scott, WK, Seeley, W, Selvackadunco, S, Simuni, T, Stadelmann, C, Svenningsson, P, Thomas, A, Trenkwalder, C, Troakes, C, Trojanowski, JQ, Uitti, RJ, White, CL, Wszolek, ZK, Xie, T, Ximelis, T, Yebenes, J, Alzheimer's Disease Genetics Consortium, Müller, U, Schellenberg, GD, Herms, J, Kuhlenbäumer, G, Höglinger, G, Hopfner, F, Tietz, AK, Ruf, VC, Ross, OA, Koga, S, Dickson, D, Aguzzi, A, Attems, J, Beach, T, Beller, A, Cheshire, WP, van Deerlin, V, Desplats, P, Deuschl, G, Duyckaerts, C, Ellinghaus, D, Evsyukov, V, Flanagan, ME, Franke, A, Frosch, MP, Gearing, M, Gelpi, E, van Gerpen, JA, Ghetti, B, Glass, JD, Grinberg, LT, Halliday, G, Helbig, I, Höllerhage, M, Huitinga, I, Irwin, DJ, Keene, DC, Kovacs, GG, Lee, EB, Levin, J, Martí, MJ, Mackenzie, I, McKeith, I, Mclean, C, Mollenhauer, B, Neumann, M, Newell, KL, Pantelyat, A, Pendziwiat, M, Peters, A, Molina Porcel, L, Rabano, A, Matěj, R, Rajput, A, Reimann, R, Scott, WK, Seeley, W, Selvackadunco, S, Simuni, T, Stadelmann, C, Svenningsson, P, Thomas, A, Trenkwalder, C, Troakes, C, Trojanowski, JQ, Uitti, RJ, White, CL, Wszolek, ZK, Xie, T, Ximelis, T, Yebenes, J, Alzheimer's Disease Genetics Consortium, Müller, U, Schellenberg, GD, Herms, J, Kuhlenbäumer, G, and Höglinger, G

Published
2022

5. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Author

Chia, R, Sabir, MS, Bandres-Ciga, S, Saez-Atienzar, S, Reynolds, RH, Gustavsson, E, Walton, RL, Ahmed, S, Viollet, C, Ding, JH, Makarious, MB, Diez-Fairen, M, Portley, MK, Shah, Z, Abramzon, Y, Hernandez, DG, Blauwendraat, C, Stone, DJ, Eicher, J, Parkkinen, L, Ansorge, O, Clark, L, Honig, LS, Marder, K, Lemstra, A, St George-Hyslop, P, Londos, E, Morgan, K, Lashley, T, Warner, TT, Jaunmuktane, Z, Galasko, D, Santana, I, Tienari, PJ, Myllykangas, L, Oinas, M, Cairns, NJ, Morris, JC, Halliday, GM, Van Deerlin, VM, Trojanowski, JQ, Grassano, M, Calvo, A, Mora, G, Canosa, A, Floris, G, Bohannan, RC, Brett, F, Gan-Or, Z, Geiger, JT, Moore, A, May, P, Kruger, R, Goldstein, DS, Lopez, G, Tayebi, N, Sidransky, E, Norcliffe-Kaufmann, L, Palma, JA, Kaufmann, H, Shakkottai, VG, Perkins, M, Newell, KL, Gasser, T, Schulte, C, Landi, F, Salvi, E, Cusi, D, Masliah, E, Kim, RC, Caraway, CA, Monuki, ES, Brunetti, M, Dawson, TM, Rosenthal, LS, Albert, MS, Pletnikova, O, Troncoso, JC, Flanagan, ME, Mao, QW, Bigio, EH, Rodriguez-Rodriguez, E, Infante, J, Lage, C, Gonzalez-Aramburu, I, Sanchez-Juan, P, Ghetti, B, Keith, J, Black, SE, Masellis, M, Rogaeva, E, Duyckaerts, C, Brice, A, Lesage, S, Xiromerisiou, G, Barrett, MJ, Tilley, BS, Gentleman, S, Logroscino, G, Serrano, GE, Beach, TG, McKeith, IG, Thomas, AJ, Attems, J, Morris, CM, Palmer, L, Love, S, Troakes, C, Al-Sarraj, S, Hodges, AK, Aarsland, D, Klein, G, Kaiser, SM, Woltjer, R, Pastor, P, Bekris, LM, Leverenz, JB, Besser, LM, Kuzma, A, Renton, AE, Goate, A, Bennett, DA, Scherzer, CR, Morris, HR, Ferrari, R, Albani, D, Pickering-Brown, S, Faber, K, Kukull, WA, Morenas-Rodriguez, E, Lleo, A, Fortea, J, Alcolea, D, Clarimon, J, Nalls, MA, Ferrucci, L, Resnick, SM, Tanaka, T, Foroud, TM, Graff-Radford, NR, Wszolek, ZK, Ferman, T, Boeve, BF, Hardy, JA, Topol, EJ, Torkamani, A, Singleton, AB, Ryten, M, Dickson, DW, Chio, A, Ross, OA, Gibbs, JR, Dalgard, CL, Traynor, BJ, Scholz, SW, and Amer Genome Ctr

Subjects
hormones, hormone substitutes, and hormone antagonists
Abstract

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Published
2021

6. Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease

Author

Leonard H, Lake J, Kim JJ, Gibbs JR, Ruskey JA, Pihlstrøm L, Eerola-Rautio J, Tienari PJ, Grosset DG, Wood N, Noyce AJ, Middlehurst B, Kia DA, Tan M, Houlden H, Storm CS, Morris HR, Plun-Favreau H, Holmans P, Hardy J, Trabzuni D, Quinn J, Bubb V, Mok KY, Kinghorn KJ, Wood NW, Lewis P, Schreglmann SR, Lovering R, R'Bibo L, Manzoni C, Rizig M, Ryten M, Guelfi S, Escott-Price V, Chelban V, Foltynie T, Williams N, Morrison KE, Clarke C, Harvey K, Jacobs BM, Brice A, Danjou F, Lesage S, Corvol JC, Martinez M, Schulte C, Brockmann K, Simón-Sánchez J, Heutink P, Rizzu P, Sharma M, Gasser T, Schneider SA, Cookson MR, Bandres-Ciga S, Blauwendraat C, Craig DW, Billingsley K, Makarious MB, Narendra DP, Faghri F, Hernandez DG, Van Keuren-Jensen K, Shulman JM, Iwaki H, Leonard HL, Nalls MA, Robak L, Bras J, Guerreiro R, Lubbe S, Troycoco T, Finkbeiner S, Mencacci NE, Lungu C, Singleton AB, Scholz SW, Reed X, Uitti RJ, Ross OA, Grenn FP, Moore A, Alcalay RN, Wszolek ZK, Gan-Or Z, Rouleau GA, Krohn L, Mufti K, van Hilten JJ, Marinus J, Adarmes-Gómez AD, Aguilar M, Alvarez I, Alvarez V, Barrero FJ, Yarza JAB, Bernal-Bernal I, Blazquez M, Bonilla-Toribio M, Botía JA, Boungiorno MT, 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 MJG, Gonzalez-Aramburu I, Pagola AG, Hoenicka J, Infante J, Jesús S, Jimenez-Escrig A, Kulisevsky J, Labrador-Espinosa MA, Lopez-Sendon JL, de Munain Arregui AL, Macias D, Torres IM, Marín J, Marti MJ, Martínez-Castrillo JC, Méndez-Del-Barrio C, González MM, Mata M, Mínguez A, Mir P, Rezola EM, Muñoz E, Pagonabarraga J, Pastor P, Errazquin FP, Periñán-Tocino T, Ruiz-Martínez J, Ruz C, Rodriguez AS, Sierra M, Suarez-Sanmartin E, Tabernero C, Tartari JP, Tejera-Parrado C, Tolosa E, Valldeoriola F, Vargas-González L, Vela L, Vives F, Zimprich A, Pihlstrom L, Toft M, Taba P, Koks S, Hassin-Baer S, Majamaa K, Siitonen A, Tienari P, Okubadejo NU, Ojo OO, Kaiyrzhanov R, Shashkin C, Zharkinbekova N, Akhmetzhanov V, Kaishybayeva G, Karimova A, Khaibullin T, Lynch TL, and International Parkinson's Disease Genomics Consortium (IPDGC)

Abstract

OBJECTIVE: Parkinson's disease (PD) is a complex neurodegenerative disorder. Men are on average ~ 1.5 times more likely to develop PD compared to women with European ancestry. Over the years, genomewide association studies (GWAS) have identified numerous genetic risk factors for PD, however, it is unclear whether genetics contribute to disease etiology in a sex-specific manner. METHODS: In an effort to study sex-specific genetic factors associated with PD, we explored 2 large genetic datasets from the International Parkinson's Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases, and 90,662 female controls. We performed GWAS meta-analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases. RESULTS: In total, 19 genomewide significant regions were identified and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWAS were identified (rg = 0.877) and heritability estimates were identical between male and female PD cases (~ 20%). INTERPRETATION: We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females cases at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus female patients. ANN NEUROL 2021;90:41-48.

Published
2021

7. Brain volumetric deficits in MAPT mutation carriers: a multisite study

Author

Chu, SA, Flagan, TM, Staffaroni, AM, Jiskoot, Lize, Deng, J, Spina, S, Zhang, L, Sturm, VE, Yokoyama, JS, Seeley, WW, Papma, Janne, Geschwind, DH, Rosen, HJ, Boeve, BF, Boxer, AL, Heuer, HW, Forsberg, LK, Brushaber, DE, Grossman, M, Coppola, G, Dickerson, BC, Bordelon, YM, Faber, K, Feldman, HH, Fields, JA, Fong, JC, Foroud, T, Gavrilova, RH, Ghoshal, N, Graff-Radford, NR, Hsiung, GYR, Huey, ED, Irwin, DJ, Kantarci, K, Kaufer, DI, Karydas, AM, Knopman, DS, Kornak, J, Kramer, JH, Kukull, WA, Lapid, MI, Litvan, I, Mackenzie, IRA, Mendez, MF, Miller, BL, Onyike, CU, Pantelyat, AY, Rademakers, R, Ramos, E, Roberson, ED, Tartaglia, M, Tatton, NA, Toga, AW, Vetor, A, Weintraub, S, Wong, B, Wszolek, ZK, van Swieten, J.C., Lee, SE, Chu, SA, Flagan, TM, Staffaroni, AM, Jiskoot, Lize, Deng, J, Spina, S, Zhang, L, Sturm, VE, Yokoyama, JS, Seeley, WW, Papma, Janne, Geschwind, DH, Rosen, HJ, Boeve, BF, Boxer, AL, Heuer, HW, Forsberg, LK, Brushaber, DE, Grossman, M, Coppola, G, Dickerson, BC, Bordelon, YM, Faber, K, Feldman, HH, Fields, JA, Fong, JC, Foroud, T, Gavrilova, RH, Ghoshal, N, Graff-Radford, NR, Hsiung, GYR, Huey, ED, Irwin, DJ, Kantarci, K, Kaufer, DI, Karydas, AM, Knopman, DS, Kornak, J, Kramer, JH, Kukull, WA, Lapid, MI, Litvan, I, Mackenzie, IRA, Mendez, MF, Miller, BL, Onyike, CU, Pantelyat, AY, Rademakers, R, Ramos, E, Roberson, ED, Tartaglia, M, Tatton, NA, Toga, AW, Vetor, A, Weintraub, S, Wong, B, Wszolek, ZK, van Swieten, J.C., and Lee, SE

Abstract

Objective: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. Methods: We studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers’ clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson’s disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. Results: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes emerged in a subset of presymptomatic carriers as early as their thirties. Low white matter volumes arose infrequently among presymptomatic carriers. Interpretation: A subset of presymptomatic MAPT mutation carriers showed low volumes in mesial temporal lobe, the region ubiquitously atrophied in all symptomatic carriers. With each decade of age, an increasing percentage of presymptomatic carriers showed low mesial temporal volume, suggestive of early neurodegeneration.

Published
2021

9. A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity (vol 138, pg 237, 2019)

Author

van der Lee, SJ, Conway, OJ, Jansen, I, Carrasquillo, MM, Kleineidam, L, van den Akker, E, Hernandez, I, van Eijk, KR, Stringa, N, Chen, JSA, Zettergren, A, Andlauer, TFM, Diez-Fairen, M, Simon-Sanchez, J, Lleo, A, Zetterberg, H, Nygaard, M, Blauwendraat, C, Savage, JE, Mengel-From, J, Moreno-Grau, S, Wagner, M, Fortea, J, Keogh, MJ, Blennow, K, Skoog, I, Friese, MA, Pletnikova, O, Zulaica, M, Lage, C, de Rojas, I, Riedel-Heller, S, Illan-Gala, I, Wei, W, Jeune, B, Orellana, A, Bergh, FT, Wang, X, Hulsman, M, Beker, N, Tesi, N, Morris, CM, Indakoetxea, B, Collij, LE, Scherer, M, Morenas-Rodriguez, E, Ironside, JW, van Berckel, BNM, Alcolea, D, Wiendl, H, Strickland, SL, Pastor, P, Rodriguez, ER, Boeve, BF, Petersen, RC, Ferman, TJ, van Gerpen, JA, Reinders, MJT, Uitti, RJ, Tarraga, L, Maier, W, Dols-Icardo, O, Kawalia, A, Dalmasso, MC, Boada, M, Zettl, UK, van Schoor, NM, Beekman, M, Allen, M, Masliah, E, de Munain, AL, Pantelyat, A, Wszolek, ZK, Ross, OA, Dickson, DW, Graff-Radford, NR, Knopman, D, Rademakers, R, Lemstra, AW, Pijnenburg, YAL, Scheltens, P, Gasser, T, Chinnery, PF, Hemmer, B, Huisman, MA, Troncoso, J, Moreno, F, Nohr, EA, Sorensen, TIA, Heutink, P, Sanchez-Juan, P, Posthuma, D, Clarim?on, J, Christensen, K, Ertekin-Taner, N, Scholz, SW, Ramirez, A, Ruiz, A, Slagboom, E, van der Flier, WM, and Holstege, H

Subjects
education
Abstract

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.

Published
2020

10. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study

Author

Moore, KM, Nicholas, J, Grossman, M, McMillan, CT, Irwin, DJ, Massimo, L, Van Deerlin, VM, Warren, JD, Fox, NC, Rossor, MN, Mead, S, Bocchetta, M, Boeve, BF, Knopman, DS, Graff-Radford, NR, Forsberg, LK, Rademakers, R, Wszolek, ZK, van Swieten, JC, Jiskoot, LC, Meeter, LH, Dopper, EGP, Papma, JM, Snowden, JS, Saxon, J, Jones, M, Pickering-Brown, S, Le Ber, I, Camuzat, A, Brice, A, Caroppo, P, Ghidoni, R, Pievani, M, Benussi, L, Binetti, G, Dickerson, BC, Lucente, D, Krivensky, S, Graff, C, Oijerstedt, L, Fallstrom, M, Thonberg, H, Ghoshal, N, Morris, JC, Borroni, B, Benussi, A, Padovani, A, Galimberti, D, Scarpini, E, Fumagalli, GG, Mackenzie, IR, Hsiung, G-YR, Sengdy, P, Boxer, AL, Rosen, H, Taylor, JB, Synofzik, M, Wilke, C, Sulzer, P, Hodges, JR, Halliday, G, Kwok, J, Sanchez-Valle, R, Llado, A, Borrego-Ecija, S, Santana, I, Almeida, MR, Tabuas-Pereira, M, Moreno, F, Barandiaran, M, Indakoetxea, B, Levin, J, Danek, A, Rowe, JB, Cope, TE, Otto, M, Anderl-Straub, S, de Mendonca, A, Maruta, C, Masellis, M, Black, SE, Couratier, P, Lautrette, G, Huey, ED, Sorbi, S, Nacmias, B, Laforce, R, Tremblay, M-PL, Vandenberghe, R, Van Damme, P, Rogalski, EJ, Weintraub, S, Gerhard, A, Onyike, CU, Ducharme, S, Papageorgiou, SG, Ng, ASL, Brodtmann, A, Finger, E, Guerreiro, R, Bras, J, Rohrer, JD, Heller, C, Convery, R, Woollacott, IOC, Shafei, R, Graff-Radford, J, Jones, DT, Dheel, CM, Savica, R, Lapid, MI, Baker, M, Fields, JA, Gavrilova, R, Domoto-Reilly, K, Poos, JM, van der Ende, EL, Panman, JL, Kaat, LD, Seelaar, H, Richardson, A, Frisoni, G, Mega, A, Fostinelli, S, Chiang, H-H, Alberici, A, Arighi, A, Fenoglio, C, Heuer, H, Miller, B, Karydas, A, Fong, J, Leitao, MJ, Santiago, B, Duro, D, Ferreira, C, Gabilondo, A, de Arriba, M, Tainta, M, Zulaica, M, Ferreira, CB, Semler, E, Ludolph, A, Landwehrmeyer, B, Volk, AE, Miltenberger, G, Verdelho, A, Afonso, S, Tartaglia, MC, Freedman, M, Rogaeva, E, Ferrari, C, Piaceri, I, Bessi, V, Lombardi, G, St-Onge, F, Dore, M-C, Bruffaerts, R, Vandenbulcke, M, Van den Stock, J, Mesulam, MM, Bigio, E, Koros, C, Papatriantafyllou, J, Kroupis, C, Stefanis, L, Shoesmith, C, Roberson, E, Coppola, G, Ramos, EMDS, Geschwind, D, Moore, KM, Nicholas, J, Grossman, M, McMillan, CT, Irwin, DJ, Massimo, L, Van Deerlin, VM, Warren, JD, Fox, NC, Rossor, MN, Mead, S, Bocchetta, M, Boeve, BF, Knopman, DS, Graff-Radford, NR, Forsberg, LK, Rademakers, R, Wszolek, ZK, van Swieten, JC, Jiskoot, LC, Meeter, LH, Dopper, EGP, Papma, JM, Snowden, JS, Saxon, J, Jones, M, Pickering-Brown, S, Le Ber, I, Camuzat, A, Brice, A, Caroppo, P, Ghidoni, R, Pievani, M, Benussi, L, Binetti, G, Dickerson, BC, Lucente, D, Krivensky, S, Graff, C, Oijerstedt, L, Fallstrom, M, Thonberg, H, Ghoshal, N, Morris, JC, Borroni, B, Benussi, A, Padovani, A, Galimberti, D, Scarpini, E, Fumagalli, GG, Mackenzie, IR, Hsiung, G-YR, Sengdy, P, Boxer, AL, Rosen, H, Taylor, JB, Synofzik, M, Wilke, C, Sulzer, P, Hodges, JR, Halliday, G, Kwok, J, Sanchez-Valle, R, Llado, A, Borrego-Ecija, S, Santana, I, Almeida, MR, Tabuas-Pereira, M, Moreno, F, Barandiaran, M, Indakoetxea, B, Levin, J, Danek, A, Rowe, JB, Cope, TE, Otto, M, Anderl-Straub, S, de Mendonca, A, Maruta, C, Masellis, M, Black, SE, Couratier, P, Lautrette, G, Huey, ED, Sorbi, S, Nacmias, B, Laforce, R, Tremblay, M-PL, Vandenberghe, R, Van Damme, P, Rogalski, EJ, Weintraub, S, Gerhard, A, Onyike, CU, Ducharme, S, Papageorgiou, SG, Ng, ASL, Brodtmann, A, Finger, E, Guerreiro, R, Bras, J, Rohrer, JD, Heller, C, Convery, R, Woollacott, IOC, Shafei, R, Graff-Radford, J, Jones, DT, Dheel, CM, Savica, R, Lapid, MI, Baker, M, Fields, JA, Gavrilova, R, Domoto-Reilly, K, Poos, JM, van der Ende, EL, Panman, JL, Kaat, LD, Seelaar, H, Richardson, A, Frisoni, G, Mega, A, Fostinelli, S, Chiang, H-H, Alberici, A, Arighi, A, Fenoglio, C, Heuer, H, Miller, B, Karydas, A, Fong, J, Leitao, MJ, Santiago, B, Duro, D, Ferreira, C, Gabilondo, A, de Arriba, M, Tainta, M, Zulaica, M, Ferreira, CB, Semler, E, Ludolph, A, Landwehrmeyer, B, Volk, AE, Miltenberger, G, Verdelho, A, Afonso, S, Tartaglia, MC, Freedman, M, Rogaeva, E, Ferrari, C, Piaceri, I, Bessi, V, Lombardi, G, St-Onge, F, Dore, M-C, Bruffaerts, R, Vandenbulcke, M, Van den Stock, J, Mesulam, MM, Bigio, E, Koros, C, Papatriantafyllou, J, Kroupis, C, Stefanis, L, Shoesmith, C, Roberson, E, Coppola, G, Ramos, EMDS, and Geschwind, D

Abstract

BACKGROUND: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. METHODS: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. FINDINGS: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49·5 years (SD 10·0; onset) and 58·5 years (11·3; death) in the MAPT group, 58·2 years (9·8; onset) and 65·3 years (10·9; death) in the C9orf72 group, and 61·3 years (8·8; onset) and 68·8 years (9·7; death) in the GRN group. Mean disease duration was 6·4 years (SD 4·9) in the C9orf72 group, 7·1 years (3·9) in the GRN group, and 9·3 years (6·4) in the MAPT group. Individual age at onset and at

Published
2020

12. Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

Author

Wang, L, Aasly, J, Annesi, G, Bardien, S, Bozi, M, Brice, A, Carr, J, Chung, S, Clarke, C, Crosiers, D, Deutschländer, A, Eckstein, G, Farrer, M, Goldwurm, S, Garraux, G, Hadjigeorgiou, G, Hicks, A, Hattori, N, Klein, C, Jeon, B, Kim, Y, Lesage, S, Lin, J, Lynch, T, Lichtner, P, Lang, A, Mok, V, Jasinska-Myga, B, Mellick, G, Morrison, K, Opala, G, Pihlstrøm, L, Pramstaller, P, Park, S, Quattrone, A, Rogaeva, E, Ross, O, Stefanis, L, Stockton, J, Silburn, P, Theuns, J, Tan, E, Tomiyama, H, Toft, M, Van Broeckhoven, C, Uitti, R, Wirdefeldt, K, Wszolek, Z, Xiromerisiou, G, Yueh, K, Zhao, Y, Gasser, T, Maraganore, D, Krüger, R, Sharma, M, Boyle, RS, Sellbach, A, O'Sullivan, JD, Sutherland, GT, Siebert, GA, Dissanayaka, NN, Pickut, B, Engelborghs, S, Meeus, B, De Deyn, PP, Cras, P, Lang, AE, Tzourio, C, Amouyel, P, Loriot, MA, Mutez, E, Duflot, A, Legendre, JP, Waucquier, N, Riess, O, Berg, D, Schulte, C, Djarmati, A, Hagenah, J, Lohman, K, Auburger, G, Hilker, R, van de Loo, S, Dardiotis, E, Tsimourtou, V, Ralli, S, Kountra, P, Patramani, G, Vogiatzi, C, Funayama, M, Yoshino, H, Li, Y, Imamichi, Y, Toda, T, Satake, W, Valente, EM, Ferraris, A, Dallapiccola, B, Ialongo, T, Brighina, L, Corradi, B, Ferrarese, C, Piolti, MR, Tarantino, P, Annesi, F, Gagliardi, M, Jeon, BS, Klodowska-Duda, G, Boczarska-Jedynak, M, Tan, EK, Belin, AC, Olson, L, Galter, D, Westerlund, M, Sydow, O, Nilsson, C, Puschmann, A, Lin, JJ, Maraganore, DM, Ahlskog, J, de Andrade, M, Lesnick, TG, Rocca, WA, Checkowa, H, Ross, OA, Wszolek, ZK, Uitti, RJ, Pathologic Biochemistry and Physiology, GEO-PD Consortium, Wang, L, Aasly, J, Annesi, G, Bardien, S, Bozi, M, Brice, A, Carr, J, Chung, S, Clarke, C, Crosiers, D, Deutschländer, A, Eckstein, G, Farrer, M, Goldwurm, S, Garraux, G, Hadjigeorgiou, G, Hicks, A, Hattori, N, Klein, C, Jeon, B, Kim, Y, Lesage, S, Lin, J, Lynch, T, Lichtner, P, Lang, A, Mok, V, Jasinska-Myga, B, Mellick, G, Morrison, K, Opala, G, Pihlstrøm, L, Pramstaller, P, Park, S, Quattrone, A, Rogaeva, E, Ross, O, Stefanis, L, Stockton, J, Silburn, P, Theuns, J, Tan, E, Tomiyama, H, Toft, M, Van Broeckhoven, C, Uitti, R, Wirdefeldt, K, Wszolek, Z, Xiromerisiou, G, Yueh, K, Zhao, Y, Gasser, T, Maraganore, D, Krüger, R, Sharma, M, Boyle, R, Sellbach, A, O'Sullivan, J, Sutherland, G, Siebert, G, Dissanayaka, N, Pickut, B, Engelborghs, S, Meeus, B, De Deyn, P, Cras, P, Tzourio, C, Amouyel, P, Loriot, M, Mutez, E, Duflot, A, Legendre, J, Waucquier, N, Riess, O, Berg, D, Schulte, C, Djarmati, A, Hagenah, J, Lohman, K, Auburger, G, Hilker, R, van de Loo, S, Dardiotis, E, Tsimourtou, V, Ralli, S, Kountra, P, Patramani, G, Vogiatzi, C, Funayama, M, Yoshino, H, Li, Y, Imamichi, Y, Toda, T, Satake, W, Valente, E, Ferraris, A, Dallapiccola, B, Ialongo, T, Brighina, L, Corradi, B, Ferrarese, C, Piolti, M, Tarantino, P, Annesi, F, Gagliardi, M, Klodowska-Duda, G, Boczarska-Jedynak, M, Belin, A, Olson, L, Galter, D, Westerlund, M, Sydow, O, Nilsson, C, Puschmann, A, Ahlskog, J, de Andrade, M, Lesnick, T, Rocca, W, and Checkowa, H

Subjects
Male, Age at onset, confidence interval, Genetic Epidemiology of Parkinson's Disease, Parkinson disease, spinocerebellar ataxia, Nerve Tissue Proteins, Disease, Biology, Parkinson Disease/epidemiology, Trinucleotide Repeat Expansion/genetics, Gene Frequency, Ataxins/genetics, Humans, Nerve Tissue Proteins/genetics, Genetic Predisposition to Disease, Risk factor, Allele frequency, Nuclear Protein, Aged, risk, Genetics, Medicine(all), Nuclear Proteins, Parkinson Disease, Ataxin, Odds ratio, Middle Aged, Phenotype, Nuclear Proteins/genetics, Genetic epidemiology, Ataxins, Gene Frequency/genetics, Nerve Tissue Protein, Peptide, Cohort, Female, Neurology (clinical), Human medicine, Trinucleotide repeat expansion, Peptides, Trinucleotide Repeat Expansion, Peptides/genetics, Human
Abstract

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson9s Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD.

Published
2015
Full Text
View/download PDF

13. Creation of an open-access, mutation-defined fibroblast resource for neurological disease research

Author

Wray, S, Self, M, Lewis, PA, Taanman, JW, Ryan, NS, Mahoney, CJ, Liang, Y, Devine, MJ, Sheerin, UM, Houlden, H, Morris, HR, Healy, D, Marti-Masso, JF, Preza, E, Barker, S, Sutherland, M, Corriveau, RA, D'Andrea, M, Schapira, AHV, Uitti, RJ, Guttman, M, Opala, G, Jasinska-Myga, B, Puschmann, A, Nilsson, C, Espay, AJ, Slawek, J, Gutmann, L, Boeve, BF, Boylan, K, Jon Stoessl, A, Ross, OA, Maragakis, NJ, Van Gerpen, J, Gerstenhaber, M, Gwinn, K, Dawson, TM, Isacson, O, Marder, KS, Clark, LN, Przedborski, SE, Finkbeiner, S, Rothstein, JD, Wszolek, ZK, Rossor, MN, Hardy, J, Gusella, JF, MacDonald, ME, Wheeler, VC, Ross, CA, Akimov, S, Arjomand, J, Thompson, LM, King, A, Hermanowicz, N, Winokur, S, Svendsen, CN, Mattis, V, Onorati, M, Cattaneo, E, Allen, ND, Kemp, PJ, Kim, KS, Przedborski, S, Feng, J, Lee, VMY, Trojanowski, JQ, James Surmeier, D, Henderson, CE, Maniatis, T, Eggan, K, and Cudowicz, ME

Abstract

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.

Published
2012
Full Text
View/download PDF

14. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy

Author

Höglinger, GU, Melhem, NM, Dickson, DW, Sleiman, PMA, Wang, LS, Klei, L, Rademakers, R, De Silva, R, Litvan, I, Riley, DE, Van Swieten, JC, Heutink, P, Wszolek, ZK, Uitti, RJ, Vandrovcova, J, Hurtig, HI, Gross, RG, Maetzler, W, Goldwurm, S, Tolosa, E, Borroni, B, Pastor, P, Cantwell, LB, Han, MR, Dillman, A, Van Der Brug, MP, Gibbs, JR, Cookson, MR, Hernandez, DG, Singleton, AB, Farrer, MJ, Yu, CE, Golbe, LI, Revesz, T, Hardy, J, Lees, AJ, Devlin, B, Hakonarson, H, Müller, U, Schellenberg, GD, Albin, RL, Alonso, E, Antonini, A, Apfelbacher, M, Arnold, SE, Avila, J, Beach, TG, Beecher, S, Berg, D, Bird, TD, Bogdanovic, N, Boon, AJW, Bordelon, Y, Brice, A, Budka, H, Canesi, M, Chiu, WZ, Cilia, R, Colosimo, C, De Deyn, PP, De Yebenes, JG, Kaat, LD, Duara, R, Durr, A, Engelborghs, S, Fabbrini, G, Finch, NA, Flook, R, Frosch, MP, Gaig, C, Galasko, DR, Gasser, T, Gearing, M, Geller, ET, Ghetti, B, Graff-Radford, NR, Grossman, M, Hall, DA, Hazrati, LN, Höllerhage, M, Jankovic, J, Juncos, JL, Karydas, A, Kretzschmar, HA, and Leber, I

Subjects
eye diseases
Abstract

Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals (P < 5 × 10-8) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved.

Published
2011
Full Text
View/download PDF

15. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

Author

Kouri, N, Ross, OA, Dombroski, B, Younkin, CS, Serie, DJ, Soto-Ortolaza, A, Baker, M, Finch, NCA, Yoon, H, Kim, J, Fujioka, S, McLean, CA, Ghetti, B, Spina, S, Cantwell, LB, Farlow, MR, Grafman, J, Huey, ED, Han, MR, Beecher, S, Geller, ET, Kretzschmar, HA, Roeber, S, Gearing, M, Juncos, JL, Vonsattel, JPG, Van Deerlin, VM, Grossman, M, Hurtig, HI, Gross, RG, Arnold, SE, Trojanowski, JQ, Lee, VM, Wenning, GK, White, CL, Hoeglinger, GU, Mueller, U, Devlin, B, Golbe, LI, Crook, J, Parisi, JE, Boeve, BF, Josephs, KA, Wszolek, ZK, Uitti, RJ, Graff-Radford, NR, Litvan, I, Younkin, SG, Wang, L-S, Ertekin-Taner, N, Rademakers, R, Hakonarsen, H, Schellenberg, GD, Dickson, DW, Kouri, N, Ross, OA, Dombroski, B, Younkin, CS, Serie, DJ, Soto-Ortolaza, A, Baker, M, Finch, NCA, Yoon, H, Kim, J, Fujioka, S, McLean, CA, Ghetti, B, Spina, S, Cantwell, LB, Farlow, MR, Grafman, J, Huey, ED, Han, MR, Beecher, S, Geller, ET, Kretzschmar, HA, Roeber, S, Gearing, M, Juncos, JL, Vonsattel, JPG, Van Deerlin, VM, Grossman, M, Hurtig, HI, Gross, RG, Arnold, SE, Trojanowski, JQ, Lee, VM, Wenning, GK, White, CL, Hoeglinger, GU, Mueller, U, Devlin, B, Golbe, LI, Crook, J, Parisi, JE, Boeve, BF, Josephs, KA, Wszolek, ZK, Uitti, RJ, Graff-Radford, NR, Litvan, I, Younkin, SG, Wang, L-S, Ertekin-Taner, N, Rademakers, R, Hakonarsen, H, Schellenberg, GD, and Dickson, DW

Abstract

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10(-12)), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10(-8)), and 2p22 at SOS1 (rs963731; P=1.76 × 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10(-7)) and MAPT H1c (17q21; rs242557; P=7.91 × 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).

Published
2015

16. Sequencing of the a-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations

Author

VAUGHAN JR, FARRER MJ, WSZOLEK ZK, GASSER T, DüRR A, AGID Y, BONIFATI V, VOLPE G, LINCOLN S, BRETELER M, MECO M, BRICE A, MARSDEN CD, HARDY J, WOOD NW, DE MICHELE, GIUSEPPE, Vaughan, Jr, Farrer, Mj, Wszolek, Zk, Gasser, T, Dürr, A, Agid, Y, Bonifati, V, DE MICHELE, Giuseppe, Volpe, G, Lincoln, S, Breteler, M, Meco, M, Brice, A, Marsden, Cd, Hardy, J, and Wood, Nw

Published
1998

17. Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease

Author

Di Fonzo, A, Tassorelli, C, De Mari, M, Chien, Hf, Ferreira, J, Rohé, Cf, Riboldazzi, G, Antonini, A, Albani, G, Mauro, A, Marconi, R, Abbruzzese, G, Lopiano, L, Fincati, E, Guidi, M, Marini, P, Stocchi, F, Onofrj, M, Toni, V, Tinazzi, M, Fabbrini, G, Lamberti, P, Vanacore, N, Meco, G, Leitner, P, Uitti, Rj, Wszolek, Zk, Gasser, T, Simons, Ej, Breedveld, Gj, Goldwurm, S, Pezzoli, G, Sampaio, C, Barbosa, E, Martignoni, E, Oostra, Ba, Bonifati, V, Vancore, N, Fabrizio, E, Locuratolo, N, Martini, L, Scoppetta, C, Colosimo, C, Manfredi, Ma, Tavella, A, Bergamasco, B, Pacchetti, C, Nappi, G, Canesi, M, Calandrella, D, Brono, G, Manfredi, Mi, Raudino, F, Corengia, E, Bonizzato, A, Ferracci, C, Dalla Libera, A, Marchese, R, Montagna, P, Ramat, S, Massaro, F, Minardi, C, Rasi, F, Thomas, A, Vacca, L, De Pandis, F, Diroma, C, Iliceto, G, Trianni, G, De Gaetano, A, Rizzo, M, and Cossu, G.

Published
2006

18. Alpha-synuclein repeat variants and survival in Parkinson's disease

Author

Chung, Sj, Biernacka, Jm, Armasu, Sm, Anderson, K, Frigerio, R, Aasly, Jo, Annesi, G, Bentivoglio, Anna Rita, Brighina, L, Chartier Harlin, M, Goldwurm, S, Hadjigeorgiou, G, Jasinska Myga, B, Jeon, B, Kim, Yj, Krüger, R, Lesage, S, Markopoulou, K, Mellick, G, Morrison, Ke, Puschmann, A, Tan, E, Crosiers, D, Theuns, J, Van Broeckhoven, C, Wirdefeldt, K, Wszolek, Zk, Elbaz, A, Maraganore, Dm, Bentivoglio, Anna Rita (ORCID:0000-0002-9663-095X), Chung, Sj, Biernacka, Jm, Armasu, Sm, Anderson, K, Frigerio, R, Aasly, Jo, Annesi, G, Bentivoglio, Anna Rita, Brighina, L, Chartier Harlin, M, Goldwurm, S, Hadjigeorgiou, G, Jasinska Myga, B, Jeon, B, Kim, Yj, Krüger, R, Lesage, S, Markopoulou, K, Mellick, G, Morrison, Ke, Puschmann, A, Tan, E, Crosiers, D, Theuns, J, Van Broeckhoven, C, Wirdefeldt, K, Wszolek, Zk, Elbaz, A, Maraganore, Dm, and Bentivoglio, Anna Rita (ORCID:0000-0002-9663-095X)

Published
2014

19. The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants

Author

Heckman, M, Elbaz, A, Soto Ortolaza, A, Serie, D, Aasly, J, Annesi, G, Auburger, G, Bacon, J, Boczarska Jedynak, M, Bozi, M, Brighina, L, Chartier Harlin, M, Dardiotis, E, Destée, A, Ferrarese, C, Ferraris, A, Fiske, B, Gispert, S, Hadjigeorgiou, G, Hattori, N, Ioannidis, J, Jasinska Myga, B, Jeon, B, Kim, Y, Klein, C, Kruger, R, Kyratzi, E, Lin, C, Lohmann, K, Loriot, M, Lynch, T, Mellick, G, Mutez, E, Opala, G, Park, S, Petrucci, S, Quattrone, A, Sharma, M, Silburn, P, Sohn, Y, Stefanis, L, Tadic, V, Tomiyama, H, Uitti, R, Valente, E, Vassilatis, D, Vilariño Güell, C, White, L, Wirdefeldt, K, Wszolek, Z, Wu, R, Xiromerisiou, G, Maraganore, D, Farrer, M, Ross, O, Heckman, MG, Soto Ortolaza, AI, Serie, DJ, Aasly, JO, Bacon, JA, FERRARESE, CARLO, Hadjigeorgiou, GM, Ioannidis, JPA, Jeon, BS, Kim, YJ, Mellick, GD, Park, SS, Silburn, PA, Sohn, YH, Uitti, RJ, Valente, EM, Vassilatis, DK, White, LR, Wszolek, ZK, Maraganore, DM, Farrer, MJ, Ross, OA, Heckman, M, Elbaz, A, Soto Ortolaza, A, Serie, D, Aasly, J, Annesi, G, Auburger, G, Bacon, J, Boczarska Jedynak, M, Bozi, M, Brighina, L, Chartier Harlin, M, Dardiotis, E, Destée, A, Ferrarese, C, Ferraris, A, Fiske, B, Gispert, S, Hadjigeorgiou, G, Hattori, N, Ioannidis, J, Jasinska Myga, B, Jeon, B, Kim, Y, Klein, C, Kruger, R, Kyratzi, E, Lin, C, Lohmann, K, Loriot, M, Lynch, T, Mellick, G, Mutez, E, Opala, G, Park, S, Petrucci, S, Quattrone, A, Sharma, M, Silburn, P, Sohn, Y, Stefanis, L, Tadic, V, Tomiyama, H, Uitti, R, Valente, E, Vassilatis, D, Vilariño Güell, C, White, L, Wirdefeldt, K, Wszolek, Z, Wu, R, Xiromerisiou, G, Maraganore, D, Farrer, M, Ross, O, Heckman, MG, Soto Ortolaza, AI, Serie, DJ, Aasly, JO, Bacon, JA, FERRARESE, CARLO, Hadjigeorgiou, GM, Ioannidis, JPA, Jeon, BS, Kim, YJ, Mellick, GD, Park, SS, Silburn, PA, Sohn, YH, Uitti, RJ, Valente, EM, Vassilatis, DK, White, LR, Wszolek, ZK, Maraganore, DM, Farrer, MJ, and Ross, OA

Published
2014

21. Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium

Author

Heckman, M, Soto Ortolaza, A, Aasly, J, Abahuni, N, Annesi, G, Bacon, J, Bardien, S, Bozi, M, Brice, A, Brighina, L, Carr, J, Chartier Harlin, M, Dardiotis, E, Dickson, D, Diehl, N, Elbaz, A, Ferrarese, C, Fiske, B, Gibson, J, Gibson, R, Hadjigeorgiou, G, Hattori, N, Ioannidis, J, Boczarska Jedynak, M, Jasinska Myga, B, Jeon, B, Kim, Y, Klein, C, Kruger, R, Kyratzi, E, Lesage, S, Lin, C, Lynch, T, Maraganore, D, Mellick, G, Mutez, E, Nilsson, C, Opala, G, Park, S, Petrucci, S, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Sohn, Y, Stefanis, L, Tadic, V, Theuns, J, Tomiyama, H, Uitti, R, Valente, E, Van Broeckhoven, C, van de Loo, S, Vassilatis, D, Vilariño Güell, C, White, L, Wirdefeldt, K, Wszolek, Z, Wu, R, Hentati, F, Farrer, M, Ross, O, Heckman, MG, Soto Ortolaza, AI, Aasly, JO, Bacon, JA, Dickson, DW, Diehl, NN, Gibson, JM, Hadjigeorgiou, GM, Ioannidis, JPA, Jeon, BS, Kim, YJ, Maraganore, DM, Mellick, GD, Park, SS, Silburn, PA, Sohn, YH, Uitti, RJ, Valente, EM, Vassilatis, DK, White, LR, Wszolek, ZK, Farrer, MJ, Ross, OA, FERRARESE, CARLO, Heckman, M, Soto Ortolaza, A, Aasly, J, Abahuni, N, Annesi, G, Bacon, J, Bardien, S, Bozi, M, Brice, A, Brighina, L, Carr, J, Chartier Harlin, M, Dardiotis, E, Dickson, D, Diehl, N, Elbaz, A, Ferrarese, C, Fiske, B, Gibson, J, Gibson, R, Hadjigeorgiou, G, Hattori, N, Ioannidis, J, Boczarska Jedynak, M, Jasinska Myga, B, Jeon, B, Kim, Y, Klein, C, Kruger, R, Kyratzi, E, Lesage, S, Lin, C, Lynch, T, Maraganore, D, Mellick, G, Mutez, E, Nilsson, C, Opala, G, Park, S, Petrucci, S, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Sohn, Y, Stefanis, L, Tadic, V, Theuns, J, Tomiyama, H, Uitti, R, Valente, E, Van Broeckhoven, C, van de Loo, S, Vassilatis, D, Vilariño Güell, C, White, L, Wirdefeldt, K, Wszolek, Z, Wu, R, Hentati, F, Farrer, M, Ross, O, Heckman, MG, Soto Ortolaza, AI, Aasly, JO, Bacon, JA, Dickson, DW, Diehl, NN, Gibson, JM, Hadjigeorgiou, GM, Ioannidis, JPA, Jeon, BS, Kim, YJ, Maraganore, DM, Mellick, GD, Park, SS, Silburn, PA, Sohn, YH, Uitti, RJ, Valente, EM, Vassilatis, DK, White, LR, Wszolek, ZK, Farrer, MJ, Ross, OA, and FERRARESE, CARLO

Abstract

Variants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease.

Published
2013

22. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

Author

Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, Williams, J, Carrasquillo, MM, Hamshere, ML, Pahwa, JS, Lupton, MK, Rubinsztein, DC, Brown, KS, Passmore, PA, McGuinness, B, Smith, AD, Kehoe, PG, Hooper, NM, Vardy, ERLC, Fox, NC, Goate, AM, Kauwe, JSK, Morris, JC, De Deyn, PP, Bass, NJ, McQuillin, A, Shaw, CE, Singleton, AB, Mühleisen, TW, Nöthen, MM, Pankratz, VS, Sando, SB, Aasly, JO, Wszolek, ZK, Dickson, DW, Graff Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, Ikram, MA, DeStefano, AL, Fitzpatrick, AL, Launer, LJ, Feulner, TM, Jonsson, PV, Bullido, MJ, ANNONI, GIORGIO, Holmans, PA, Younkin, SG, Owen, MJ, Williams, J., Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, Williams, J, Carrasquillo, MM, Hamshere, ML, Pahwa, JS, Lupton, MK, Rubinsztein, DC, Brown, KS, Passmore, PA, McGuinness, B, Smith, AD, Kehoe, PG, Hooper, NM, Vardy, ERLC, Fox, NC, Goate, AM, Kauwe, JSK, Morris, JC, De Deyn, PP, Bass, NJ, McQuillin, A, Shaw, CE, Singleton, AB, Mühleisen, TW, Nöthen, MM, Pankratz, VS, Sando, SB, Aasly, JO, Wszolek, ZK, Dickson, DW, Graff Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, Ikram, MA, DeStefano, AL, Fitzpatrick, AL, Launer, LJ, Feulner, TM, Jonsson, PV, Bullido, MJ, ANNONI, GIORGIO, Holmans, PA, Younkin, SG, Owen, MJ, and Williams, J.

Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10). © 2011 Nature America, Inc. All rights reserved.

Published
2011

23. Translation initiator EIF4G1 mutations in familial Parkinson disease

Author

Chartier Harlin, M, Dachsel, Jc, Vilariño Güell, C, Lincoln, Sj, Leprêtre, F, Hulihan, Mm, Kachergus, J, Milnerwood, Aj, Tapia, L, Song, M, Le Rhun, E, Mutez, E, Larvor, L, Duflot, A, Vanbesien Mailliot, C, Kreisler, A, Ross, Oa, Nishioka, K, Soto Ortolaza, Ai, Cobb, Sa, Melrose, Hl, Behrouz, B, Keeling, Bh, Bacon, Ja, Hentati, E, Williams, L, Yanagiya, A, Sonenberg, N, Lockhart, Pj, Zubair, Ac, Uitti, Rj, Aasly, Jo, Krygowska Wajs, A, Opala, G, Wszolek, Zk, Frigerio, R, Maraganore, Dm, Gosal, D, Lynch, T, Hutchinson, M, Bentivoglio, Anna Rita, Valente, Enza Maria, Nichols, Wc, Pankratz, N, Foroud, T, Gibson, Ra, Hentati, F, Dickson, Dw, Destée, A, Farrer, Mj, Bentivoglio, Anna Rita (ORCID:0000-0002-9663-095X), Chartier Harlin, M, Dachsel, Jc, Vilariño Güell, C, Lincoln, Sj, Leprêtre, F, Hulihan, Mm, Kachergus, J, Milnerwood, Aj, Tapia, L, Song, M, Le Rhun, E, Mutez, E, Larvor, L, Duflot, A, Vanbesien Mailliot, C, Kreisler, A, Ross, Oa, Nishioka, K, Soto Ortolaza, Ai, Cobb, Sa, Melrose, Hl, Behrouz, B, Keeling, Bh, Bacon, Ja, Hentati, E, Williams, L, Yanagiya, A, Sonenberg, N, Lockhart, Pj, Zubair, Ac, Uitti, Rj, Aasly, Jo, Krygowska Wajs, A, Opala, G, Wszolek, Zk, Frigerio, R, Maraganore, Dm, Gosal, D, Lynch, T, Hutchinson, M, Bentivoglio, Anna Rita, Valente, Enza Maria, Nichols, Wc, Pankratz, N, Foroud, T, Gibson, Ra, Hentati, F, Dickson, Dw, Destée, A, Farrer, Mj, and Bentivoglio, Anna Rita (ORCID:0000-0002-9663-095X)

Abstract

Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.

Published
2011

24. Independent and joint effects of the MAPT and SNCA genes in Parkinson disease

Author

Elbaz, A, Ross, Oa, Ioannidis, Jp, Soto Ortolaza, Ai, Aasly, J, Bozi, M, Chartier Harlin, Mc, Destée, A, Ferrarese, C, Ferraris, A, Gibson, Jm, Hadjigeorgiou, Gm, Jasinska Myga, B, Klein C, Krüger R, Lohmann, K, Loriot, Ma, Mellick, Gd, Mutez, E, Nilsson, C, Puschmann, A, Quattrone, A, Sharma, M, Silburn, Pa, Stefanis, L, Valente, Em, Vilariño Güell, C, Wirdefeldt, K, Wszolek, Zk, Xiromerisiou, G, Farrer, Mj, Amouyel, P, Tzourio, C, Mulot, C, Bacon, Ja, Cobb, Sa, Sutherland, Gt, Siebert, Ga, Dissanayaka, N, O'Sullivan, Jd, Boyle, R, Bordet, R, Legendre, Jp, Auburger, G, Abahuni, N, Winkler, S, Gasser, T, Riess, O, Berg, D, Schulte, C, Vassilatis, D, Stamboulis, E, Dardiotis, E, Patramani, I, Kountra, Pm, Vogiatzi, C, Markou, K, Tarantino, P, Annesi, F, Bentivoglio, Anna Rita, Guidubaldi, Arianna, Caccialupi, M, De Nigris, Francesca, Pedersen, Nl, Reimer, J, Lash, J, Searcy, J, Strongosky, A., Bentivoglio, Anna Rita (ORCID:0000-0002-9663-095X), Elbaz, A, Ross, Oa, Ioannidis, Jp, Soto Ortolaza, Ai, Aasly, J, Bozi, M, Chartier Harlin, Mc, Destée, A, Ferrarese, C, Ferraris, A, Gibson, Jm, Hadjigeorgiou, Gm, Jasinska Myga, B, Klein C, Krüger R, Lohmann, K, Loriot, Ma, Mellick, Gd, Mutez, E, Nilsson, C, Puschmann, A, Quattrone, A, Sharma, M, Silburn, Pa, Stefanis, L, Valente, Em, Vilariño Güell, C, Wirdefeldt, K, Wszolek, Zk, Xiromerisiou, G, Farrer, Mj, Amouyel, P, Tzourio, C, Mulot, C, Bacon, Ja, Cobb, Sa, Sutherland, Gt, Siebert, Ga, Dissanayaka, N, O'Sullivan, Jd, Boyle, R, Bordet, R, Legendre, Jp, Auburger, G, Abahuni, N, Winkler, S, Gasser, T, Riess, O, Berg, D, Schulte, C, Vassilatis, D, Stamboulis, E, Dardiotis, E, Patramani, I, Kountra, Pm, Vogiatzi, C, Markou, K, Tarantino, P, Annesi, F, Bentivoglio, Anna Rita, Guidubaldi, Arianna, Caccialupi, M, De Nigris, Francesca, Pedersen, Nl, Reimer, J, Lash, J, Searcy, J, Strongosky, A., and Bentivoglio, Anna Rita (ORCID:0000-0002-9663-095X)

Abstract

OBJECTIVE: We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. METHODS: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach. RESULTS: Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3' end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. INTERPRETATION: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects.

Published
2011

28. Genetic variants of α-synuclein are not associated with essential tremor.

Author

Ross OA, Conneely KN, Wang T, Vilarino-Guell C, Soto-Ortolaza AI, Rajput A, Wszolek ZK, Uitti RJ, Louis ED, Clark LN, Farrer MJ, Testa CM, Ross, Owen A, Conneely, Karen N, Wang, Tao, Vilarino-Guell, Carles, Soto-Ortolaza, Alexandra I, Rajput, Alex, Wszolek, Zbigniew K, and Uitti, Ryan J

Abstract

Background: Given the overlap between Parkinson's disease and essential tremor, we examined genetic variants in α-synuclein (SNCA) as risk determinants for essential tremor.Methods: Samples from 661 essential tremor subjects and 1316 control subjects from 4 participating North American sites were included in this study. Parkinson's disease samples (n = 427) were compared against controls. Twenty variants were selected for association analysis within the SNCA locus. Individual logistic regression analyses against essential tremor diagnosis were run for each variant and then combined using meta-analysis.Results: Our results do not show a significant association between variants in the SNCA locus and risk of essential tremor, whereas the established association of SNCA variants with Parkinson's disease risk was observed.Conclusions: Whereas genetic factors are likely to play a large role in essential tremor pathogenesis, our results do not support a role for common SNCA genetic variants in risk for essential tremor. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

32. The c.-237_236GA>TT THAP1 sequence variant does not increase risk for primary dystonia.

Author

Xiao J, Zhao Y, Bastian RW, Perlmutter JS, Racette BA, Tabbal SD, Karimi M, Paniello RC, Wszolek ZK, Uitti RJ, Van Gerpen JA, Simon DK, Tarsy D, Hedera P, Truong DD, Frei KP, Blitzer A, Rudzinska M, Pfeiffer RF, and Le C

Abstract

Background: Sequence variants in coding and noncoding regions of THAP1 have been associated with primary dystonia.Methods: In this study, 1,446 Caucasian subjects with mainly adult-onset primary dystonia and 1,520 controls were genotyped for a variant located in the 5'-untranslated region of THAP1 (c.-237_236GA>TT).Results: Minor allele frequencies were 62/2892 (2.14%) and 55/3040 (1.81%) in subjects with dystonia and controls, respectively (P=0.202). Subgroup analyses by gender and anatomical distribution also failed to attain statistical significance. In addition, there was no effect of the TT variant on expression levels of THAP1 transcript or protein.Discussion: Our findings indicate that the c.-237_236GA>TT THAP1 sequence variant does not increase risk for adult-onset primary dystonia in Caucasians. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

33. Replication of BIN1 association with Alzheimer's disease and evaluation of genetic interactions.

Author

Carrasquillo MM, Belbin O, Hunter TA, Ma L, Bisceglio GD, Zou F, Crook JE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC, Morgan K, Younkin SG, Carrasquillo, Minerva M, Belbin, Olivia, and Hunter, Talisha A

Abstract

The most recent late-onset Alzheimer's disease (LOAD) genome-wide association study revealed genome-wide significant association of two new loci: rs744373 near BIN1 (p = 1.6 × 10-11) and rs597668 near EXOC3L2/BLOC1S3/MARK4 (p = 6.5 × 10-9). We have genotyped these variants in a large (3,287 LOAD, 4,396 controls), independent dataset comprising eleven case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and also tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE ε4 status. Meta-analysis results showed no evidence of series heterogeneity and logistic regression analysis successfully replicated the association of BIN1 (rs744373) with LOAD with an odds ratio (OR = 1.17, p = 1.1 × 10-4) comparable to that previously reported (OR = 1.15). The variant near EXOC3L2 (rs597668) showed only suggestive association with LOAD (p = 0.09) after correcting for the presence of the APOE ε4 allele. Addition of our follow-up data to the results previously reported increased the strength of evidence for association with BIN1 (11,825 LOAD, 32,570 controls, rs744373 Fisher combined p = 3.8 × 10-20). We also tested for epistatic interaction between these variants and APOE ε4 as well as with the previously replicated LOAD GWAS genes (CLU: rs11136000, CR1: rs3818361, and PICALM: rs3851179). No significant interactions between these genes were detected. In summary, we provide additional evidence for the variant near BIN1 (rs744373) as a LOAD risk modifier, but our results indicate that the effect of EXOC3L2 independent of APOE ε4 should be studied further. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

41. FGF20 and Parkinson's disease: no evidence of association or pathogenicity via alpha-synuclein expression.

Author

Wider C, Dachsel JC, Soto AI, Heckman MG, Diehl NN, Yue M, Lincoln S, Aasly JO, Haugarvoll K, Trojanowski JQ, Papapetropoulos S, Mash D, Rajput A, Rajput AH, Gibson JM, Lynch T, Dickson DW, Uitti RJ, Wszolek ZK, and Farrer MJ

Abstract

Genetic variation in fibroblast growth factor 20 (FGF20) has been associated with risk of Parkinson's disease (PD). Functional evidence suggested the T allele of one SNP, rs12720208 C/T, altered PD risk by increasing FGF20 and alpha-synuclein protein levels. Herein we report our association study of FGF20 and PD risk in four patient-control series (total: 1,262 patients and 1,881 controls), and measurements of FGF20 and alpha-synuclein protein levels in brain samples (nine patients). We found no evidence of association between FGF20 variability and PD risk, and no relationship between the rs12720208 genotype, FGF20 and alpha-synuclein protein levels. [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

44. Lrrk2 and Lewy body disease.

Author

Ross OA, Toft M, Whittle AJ, Johnson JL, Papapetropoulos S, Mash DC, Litvan I, Gordon MF, Wszolek ZK, Farrer MJ, and Dickson DW

Published
2006

48. MEIS1 p.R272H in familial restless legs syndrome.

Author

Vilariño-Güell C, Chai H, Keeling BH, Young JE, Rajput A, Lynch T, Aasly JO, Uitti RJ, Wszolek ZK, Farrer MJ, Lin SC, Vilariño-Güell, C, Chai, H, Keeling, B H, Young, J E, Rajput, A, Lynch, T, Aasly, J O, Uitti, R J, and Wszolek, Z K

Published
2009
Full Text
View/download PDF

49. Essential tremor: predictors of disease progression in a clinical cohort.

Author

Putzke JD, Whaley NR, Baba Y, Wszolek ZK, Uitti RJ, Putzke, J D, Whaley, N R, Baba, Y, Wszolek, Z K, and Uitti, R J

Abstract

Objectives: To examine the utility of baseline factors to predict disease progression among a clinical cohort of patients diagnosed with essential tremor.Measures: Tremor Rating Scale (TRS).Methods: A clinical series of 128 consecutive patients diagnosed with essential tremor was included for study. 45 (35%) patients had at least one follow-up exam (mean = 3.6 years). Baseline predictive factors examined included age, age at onset of symptoms, disease duration, sex, handedness, total tremor rating score, asymmetric tremor ratings, location of initial tremor onset, use of drugs for movement disorders, ETOH responsiveness of tremor, association of head or neck tremor, history of depression, familial history of essential tremor, Parkinson's disease, Alzheimer's disease and other movement disorders.Results: On average, the TRS total score increased by <1 point per year before the first visit to the clinic and by about 2 points per year during the observed study period. The increase of 2 points per year during the observed study period represented an approximate 12% annual change from the mean TRS total score at the first clinic visit. Significant (p<0.05) predictive factors associated with increased tremor severity at the initial clinic visit included older age, longer disease duration, use of movement disorder drugs and the presence of voice tremor (r = 0.24, 0.27, 0.25, 0.19). The major factors associated with an increase in tremor severity from the initial clinic visit to the last follow up included asymmetrical tremor ratings, unilateral initial tremor onset and longer follow-up duration (r = 0.32, 0.31, 0.30). Multivariate regression analysis accounted for about 17-30% of the variance in tremor ratings (p<0.05).Conclusion: Essential tremor is a slow, progressive disease. The rate of disease progression and the factors associated with disease progression may vary throughout the disease course. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results