Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy
Günter U. Höglinger,Nadine M. Melhem,Dennis W. Dickson,Patrick M. A. Sleiman,Li-San Wang,Lambertus Klei,Rosa Rademakers,Rohan de Silva,Irene Litvan,David E. Riley,John C. van Swieten,Peter Heutink,Zbigniew K. Wszolek,Ryan J. Uitti,Jana Vandrovcova,Howard I. Hurtig,Rachel G. Gross,Walter Maetzler,Stefano Goldwurm,Eduardo Tolosa,Barbara Borroni,Pau Pastor,Laura B. Cantwell,Mi Ryung Han,Allissa Dillman,Marcel P. van der Brug,J. Raphael Gibbs,J. Raphael Gibbs,Mark R. Cookson,Dena G. Hernandez,Dena G. Hernandez,Andrew B. Singleton,Matthew J. Farrer,Chang En Yu,Lawrence I. Golbe,Tamas Revesz,John Hardy,Andrew J. Lees,Bernie Devlin,Hakon Hakonarson,Ulrich Müller,Gerard D. Schellenberg,Roger L. Albin,Elena Alonso,Angelo Antonini,Manuela Apfelbacher,Steven E. Arnold,Jesús Avila,Thomas G. Beach,Sherry Beecher,Daniela Berg,Thomas D. Bird,Nenad Bogdanovic,Agnita J.W. Boon,Yvette Bordelon,Alexis Brice,Alexis Brice,Herbert Budka,Margherita Canesi,Wang Zheng Chiu,Roberto Cilia,Carlo Colosimo,Peter Paul De Deyn,Justo Garcãa De Yebenes,Laura Donker Kaat,Ranjan Duara,Alexandra Durr,Alexandra Durr,Sebastiaan Engelborghs,Giovanni Fabbrini,Nicole A. Finch,Robyn Flook,Matthew P. Frosch,Carles Gaig,Douglas Galasko,Thomas Gasser,Marla Gearing,Evan T. Geller,Bernardino Ghetti,Neill R. Graff-Radford,Murray Grossman,Deborah A. Hall,Lili-Naz Hazrati,Matthias Höllerhage,Joseph Jankovic,Jorge L. Juncos,Anna Karydas,Hans A. Kretzschmar,Isabelle Leber,Isabelle Leber,Virginia M.-Y. Lee,Andrew P. Lieberman,Kelly E. Lyons,Claudio Mariani,Eliezer Masliah,Luke A. Massey,Catriona McLean,Nicoletta Meucci,Bruce L. Miller,Brit Mollenhauer,Jens Carsten Möller,Huw R. Morris,Christopher Morris,Sean S. O'Sullivan,Wolfgang H. Oertel,Donatella Ottaviani,Alessandro Padovani,Rajesh Pahwa,Gianni Pezzoli,Stuart Pickering-Brown,Werner Poewe,Alberto Rábano,Alex Rajput,Stephen G. Reich,Gesine Respondek,Sigrun Roeber,Jonathan D. Rohrer,Owen A. Ross,Martin N. Rossor,Giorgio Sacilotto,William W. Seeley,Klaus Seppi,Laura Silveira-Moriyama,Salvatore Spina,Karin Srulijes,Peter St George-Hyslop,Maria Stamelou,David G. Standaert,Silvana Tesei,Wallace W. Tourtellotte,Claudia Trenkwalder,Claire Troakes,John Q. Trojanowski,Juan C. Troncoso,Vivianna M. Van Deerlin,Jean Paul G. Vonsattel,Gregor K. Wenning,Charles L. White,Pia Winter,Chris Zarow,Anna Zecchinelli +140 more
TLDR
Two independent variants in MAPT affecting risk for PSP are confirmed, one of which influences MAPT brain expression and the genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface and for a myelin structural component.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.read more
Citations
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Journal ArticleDOI
Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria
Günter U. Höglinger,Gesine Respondek,Maria Stamelou,Carolin Kurz,Keith A. Josephs,Anthony E. Lang,Brit Mollenhauer,Ulrich Müller,Christer Nilsson,Jennifer L. Whitwell,Thomas Arzberger,Elisabet Englund,Ellen Gelpi,Armin Giese,David J. Irwin,Wassilios G. Meissner,Wassilios G. Meissner,Alexander Pantelyat,Alex Rajput,John C. van Swieten,Claire Troakes,Angelo Antonini,Kailash P. Bhatia,Yvette Bordelon,Yaroslau Compta,Jean-Christophe Corvol,Carlo Colosimo,Dennis W. Dickson,Richard Dodel,Leslie W. Ferguson,Murray Grossman,Jan Kassubek,Florian Krismer,Johannes Levin,Stefan Lorenzl,Huw R. Morris,Peter J. Nestor,Wolfgang H. Oertel,Werner Poewe,Gil D. Rabinovici,James B. Rowe,Gerard D. Schellenberg,Klaus Seppi,Thilo van Eimeren,Gregor K. Wenning,Adam L. Boxer,Lawrence I. Golbe,Irene Litvan +47 more
TL;DR: Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome.
Journal ArticleDOI
Tau pathology and neurodegeneration
TL;DR: The pathway leading from soluble and monomeric to hyperphosphorylated, insoluble and filamentous tau protein is at the centre of many human neurodegenerative diseases, collectively referred to as tauopathies.
Journal ArticleDOI
The impact of the unfolded protein response on human disease
Shiyu Wang,Randal J. Kaufman +1 more
TL;DR: The unfolded protein response is an essential adaptive intracellular signaling pathway that responds to metabolic, oxidative stress, and inflammatory response pathways and is implicated in a variety of diseases including metabolic disease, neurodegenerative disease, inflammatory disease, and cancer.
Journal ArticleDOI
The Role of Endoplasmic Reticulum Stress in Human Pathology
Scott A. Oakes,Feroz R. Papa +1 more
TL;DR: Chronic ER stress and defects in UPR signaling are emerging as key contributors to a growing list of human diseases, including diabetes, neurodegeneration, and cancer, and there is much interest in targeting components of the UPR as a therapeutic strategy to combat these ER stress-associated pathologies.
Journal ArticleDOI
Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
Aysu Okbay,Bart M. L. Baselmans,Jan-Emmanuel De Neve,Patrick Turley,Michel G. Nivard,Mark Alan Fontana,S. Fleur W. Meddens,S. Fleur W. Meddens,S. Fleur W. Meddens,Richard Karlsson Linnér,Richard Karlsson Linnér,Richard Karlsson Linnér,Cornelius A. Rietveld,Jaime Derringer,Jacob Gratten,James J. Lee,Jimmy Z. Liu,Ronald de Vlaming,Tarunveer S. Ahluwalia,Tarunveer S. Ahluwalia,Jadwiga Buchwald,Alana Cavadino,Alexis C. Frazier-Wood,Nicholas A. Furlotte,Victoria Garfield,Marie Henrike Geisel,Juan R. González,Saskia Haitjema,Robert Karlsson,Sander W. van der Laan,Karl-Heinz Ladwig,Jari Lahti,Sven J. van der Lee,Penelope A. Lind,Tian Liu,Lindsay K. Matteson,Evelin Mihailov,Michael B. Miller,Camelia C. Minică,Ilja M. Nolte,Dennis O. Mook-Kanamori,Peter J. van der Most,Christopher Oldmeadow,Yong Qian,Olli T. Raitakari,Olli T. Raitakari,Rajesh Rawal,Anu Realo,Anu Realo,Rico Rueedi,Rico Rueedi,Börge Schmidt,Albert V. Smith,Evie Stergiakouli,Toshiko Tanaka,Kent D. Taylor,Gudmar Thorleifsson,Juho Wedenoja,Juergen Wellmann,Harm-Jan Westra,Sara M. Willems,Wei Zhao,Najaf Amin,Andrew Bakshi,Sven Bergmann,Sven Bergmann,Gyda Bjornsdottir,Patricia A. Boyle,Samantha Cherney,Simon R. Cox,Gail Davies,Oliver S. P. Davis,Jun Ding,Nese Direk,Peter Eibich,Peter Eibich,Rebecca T. Emeny,Ghazaleh Fatemifar,Jessica D. Faul,Luigi Ferrucci,Andreas J. Forstner,Christian Gieger,Richa Gupta,Tamara B. Harris,Juliette Harris,Elizabeth G. Holliday,Jouke-Jan Hottenga,Philip L. De Jager,Philip L. De Jager,Philip L. De Jager,Marika Kaakinen,Marika Kaakinen,Eero Kajantie,Eero Kajantie,Ville Karhunen,Ivana Kolcic,Meena Kumari,Lenore J. Launer,Lude Franke,Ruifang Li-Gao,David C. Liewald,Marisa Koini,Anu Loukola,Pedro Marques-Vidal,Grant W. Montgomery,Miriam A. Mosing,Lavinia Paternoster,Alison Pattie,K. Petrovic,Laura Pulkki-Råback,Lydia Quaye,Katri Räikkönen,Igor Rudan,Rodney J. Scott,Jennifer A. Smith,Angelina R. Sutin,Angelina R. Sutin,Maciej Trzaskowski,Maciej Trzaskowski,Anna A. E. Vinkhuyzen,Lei Yu,Delilah Zabaneh,John Attia,David A. Bennett,Klaus Berger,Lars Bertram,Lars Bertram,Dorret I. Boomsma,Harold Snieder,Shun-Chiao Chang,Francesco Cucca,Ian J. Deary,Cornelia M. van Duijn,Johan G. Eriksson,Johan G. Eriksson,Ute Bültmann,Eco J. C. de Geus,Patrick J. F. Groenen,Vilmundur Gudnason,Torben Hansen,C.A. Hartman,Claire M. A. Haworth,Caroline Hayward,Andrew C. Heath,David A. Hinds,Elina Hyppönen,Elina Hyppönen,William G. Iacono,Marjo-Riitta Järvelin,Karl-Heinz Jöckel,Jaakko Kaprio,Jaakko Kaprio,Sharon L.R. Kardia,Liisa Keltikangas-Järvinen,Peter Kraft,Laura D. Kubzansky,Terho Lehtimäki,Patrik K. E. Magnusson,Nicholas G. Martin,Matt McGue,Andres Metspalu,Melinda Mills,Renée de Mutsert,Albertine J. Oldehinkel,Gerard Pasterkamp,Nancy L. Pedersen,Robert Plomin,Ozren Polasek,Christine Power,Stephen S. Rich,Frits R. Rosendaal,Hester M. den Ruijter,David Schlessinger,Helena Schmidt,Rauli Svento,Reinhold Schmidt,Behrooz Z. Alizadeh,Thorkild I. A. Sørensen,Thorkild I. A. Sørensen,Tim D. Spector,John M. Starr,Kari Stefansson,Kari Stefansson,Andrew Steptoe,Antonio Terracciano,Antonio Terracciano,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Roy Thurik,Nicholas J. Timpson,Henning Tiemeier,André G. Uitterlinden,Peter Vollenweider,Gert G. Wagner,Gert G. Wagner,Gert G. Wagner,David R. Weir,Jian Yang,Dalton Conley,George Davey Smith,Albert Hofman,Albert Hofman,Magnus Johannesson,David Laibson,Sarah E. Medland,Michelle N. Meyer,Michelle N. Meyer,Joseph K. Pickrell,Tõnu Esko,Robert F. Krueger,Jonathan P. Beauchamp,Philipp Koellinger,Philipp Koellinger,Philipp Koellinger,Daniel J. Benjamin,Meike Bartels,David Cesarini +216 more
TL;DR: In this paper, the authors conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n= 161,460), and neuroticism(n = 170,911).
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