Journal ArticleDOI
Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
Wataru Satake,Yuko Nakabayashi,Yuko Nakabayashi,Ikuko Mizuta,Ikuko Mizuta,Yushi Hirota,Yushi Hirota,Chiyomi Ito,Chiyomi Ito,Michiaki Kubo,Takahisa Kawaguchi,Tatsuhiko Tsunoda,Masahiko Watanabe,Atsushi Takeda,Hiroyuki Tomiyama,Kenji Nakashima,Kazuko Hasegawa,Fumiya Obata,Takeo Yoshikawa,Hideshi Kawakami,Saburo Sakoda,Mitsutoshi Yamamoto,Nobutaka Hattori,Miho Murata,Yusuke Nakamura,Tatsushi Toda,Tatsushi Toda +26 more
Reads0
Chats0
TLDR
The results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.Abstract:
To identify susceptibility variants for Parkinson's disease (PD), we performed a genome-wide association study (GWAS) and two replication studies in a total of 2,011 cases and 18,381 controls from Japan. We identified a new susceptibility locus on 1q32 (P = 1.52 x 10(-12)) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 x 10(-9)). We also detected strong associations at SNCA on 4q22 (P = 7.35 x 10(-17)) and LRRK2 on 12q12 (P = 2.72 x 10(-8)), both of which are implicated in autosomal dominant forms of parkinsonism. By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences. Our results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.read more
Citations
More filters
Journal ArticleDOI
Genome-wide association study reveals genetic risk underlying Parkinson's disease
Javier Simón-Sánchez,Claudia Schulte,Jose Bras,Jose Bras,Manu Sharma,J. Raphael Gibbs,J. Raphael Gibbs,Daniela Berg,Coro Paisán-Ruiz,Peter Lichtner,Sonja W. Scholz,Sonja W. Scholz,Dena G. Hernandez,Dena G. Hernandez,Rejko Krüger,Monica Federoff,Christine Klein,Alison Goate,Joel S. Perlmutter,Michael Bonin,Mike A. Nalls,Thomas Illig,Christian Gieger,Henry Houlden,Michael Steffens,Michael S. Okun,Brad A. Racette,Mark R. Cookson,Kelly D. Foote,Hubert H. Fernandez,Bryan J. Traynor,Stefan Schreiber,Sampath Arepalli,Ryan R. Zonozi,Katrina Gwinn,Marcel P. van der Brug,Marcel P. van der Brug,Grisel Lopez,Stephen J. Chanock,Arthur Schatzkin,Yikyung Park,Albert R. Hollenbeck,Jianjun Gao,Xuemei Huang,Nicholas W. Wood,Delia Lorenz,Günther Deuschl,Honglei Chen,Olaf Riess,John Hardy,Andrew B. Singleton,Thomas Gasser +51 more
TL;DR: It is demonstrated that an unequivocal role for common genetic variants in the etiology of typical PD and population-specific genetic heterogeneity in this disease is suggested, and supporting evidence that common variation around LRRK2 modulates risk for PD is provided.
Journal ArticleDOI
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
Mike A. Nalls,Nathan Pankratz,Christina M. Lill,Chuong B. Do,Dena G. Hernandez,Dena G. Hernandez,Mohamad Saad,Mohamad Saad,Mohamad Saad,Anita L. DeStefano,Anita L. DeStefano,Eleanna Kara,Jose Bras,Manu Sharma,Claudia Schulte,Margaux F. Keller,Sampath Arepalli,Christopher Letson,Connor Edsall,Hreinn Stefansson,Xinmin Liu,Hannah A. Pliner,Joseph H. Lee,Rong Cheng,M. Arfan Ikram,John P. A. Ioannidis,Georgios M. Hadjigeorgiou,Joshua C. Bis,Maria Martinez,Maria Martinez,Joel S. Perlmutter,Alison Goate,Karen Marder,Brian K. Fiske,Margaret Sutherland,Georgia Xiromerisiou,Richard H. Myers,Lorraine N. Clark,Kari Stefansson,John Hardy,Peter Heutink,Honglei Chen,Nicholas W. Wood,Henry Houlden,Haydeh Payami,Alexis Brice,Alexis Brice,William K. Scott,Thomas Gasser,Lars Bertram,Nicholas Eriksson,Tatiana Foroud,Andrew B. Singleton +52 more
TL;DR: This article conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls.
Journal ArticleDOI
100 years of Lewy pathology
TL;DR: The relevance of Lewy's discovery 100 years ago for the current understanding of PD and related disorders is reviewed.
Journal ArticleDOI
Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.
Mike A. Nalls,Vincent Plagnol,Dena G. Hernandez,Manu Sharma,Una-Marie Sheerin,Mohamad Saad,J Simón-Sánchez,Claudia Schulte,Suzanne Lesage,Suzanne Lesage,Sigurlaug Sveinbjörnsdóttir,K. Stefansson,Maria Martinez,Maria Martinez,John Hardy,Peter Heutink,Alexis Brice,Thomas Gasser,Andrew B. Singleton,Nicholas W. Wood +19 more
TL;DR: These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.
Journal ArticleDOI
Epidemiology and etiology of Parkinson’s disease: a review of the evidence
Karin Wirdefeldt,Hans-Olov Adami,Hans-Olov Adami,Philip A. Cole,Dimitrios Trichopoulos,Jack S. Mandel +5 more
TL;DR: Studies that assessed possible shared etiological components between PD and other diseases show that REM sleep behavior disorder and mental illness increase PD risk and that PD patients have lower cancer risk, but methodological concerns exist.
References
More filters
Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI
Haploview: analysis and visualization of LD and haplotype maps
TL;DR: Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface.
Journal ArticleDOI
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Paul Burton,David Clayton,Lon R. Cardon,Nicholas John Craddock,Panos Deloukas,Audrey Duncanson,Dominic P. Kwiatkowski,Mark I. McCarthy,Willem H. Ouwehand,Nilesh J. Samani,John A. Todd,Peter Donnelly,Jeffrey C. Barrett,Dan Davison,Doug Easton,David M. Evans,H. T. Leung,Jonathan Marchini,Andrew P. Morris,Chris C. A. Spencer,Martin D. Tobin,Antony P. Attwood,James P. Boorman,Barbara Cant,Ursula Everson,Judith M. Hussey,Jennifer Jolley,Alexandra S. Knight,Kerstin Koch,Elizabeth Meech,Sarah Nutland,Christopher Prowse,Helen Stevens,Niall C. Taylor,Graham R. Walters,Neil Walker,Nicholas A. Watkins,Thilo Winzer,Richard Jones,Wendy L. McArdle,Susan M. Ring,David P. Strachan,Marcus Pembrey,Gerome Breen,David St Clair,Sian Caesar,Katherine Gordon-Smith,Lisa Jones,Christine Fraser,Elaine K. Green,Detelina Grozeva,Marian L. Hamshere,Peter Holmans,Ian Jones,George Kirov,Valentina Moskvina,Ivan Nikolov,Michael Conlon O'Donovan,Michael John Owen,David A. Collier,Amanda Elkin,Anne Farmer,Richard Williamson,Peter McGuffin,Allan H. Young,I. Nicol Ferrier,Stephen G. Ball,Anthony J. Balmforth,Jennifer H. Barrett,D. Timothy Bishop,Mark M. Iles,Azhar Maqbool,Nadira Yuldasheva,Alistair S. Hall,Peter S. Braund,Richard J. Dixon,Massimo Mangino,Suzanne Stevens,John R. Thompson,Francesca Bredin,Mark Tremelling,Miles Parkes,Hazel E. Drummond,Charlie W. Lees,Elaine R. Nimmo,Jack Satsangi,Sheila A. Fisher,Alastair Forbes,Cathryn M. Lewis,Clive M. Onnie,Natalie J. Prescott,Jeremy D. Sanderson,Christopher G. Mathew,Jamie Barbour,M. Khalid Mohiuddin,Catherine E. Todhunter,John C. Mansfield,Tariq Ahmad,Fraser Cummings,Derek P. Jewell,John Webster,Morris J. Brown,G. Mark Lathrop,John M. C. Connell,Anna F. Dominiczak,Carolina A. Braga Marcano,Beverley Burke,Richard Dobson,Johannie Gungadoo,Kate L. Lee,Patricia B. Munroe,Stephen Newhouse,Abiodun Onipinla,Chris Wallace,Mingzhan Xue,Mark J. Caulfield,Martin Farrall,Anne Barton,Ian N. Bruce,Hannah Donovan,Steve Eyre,Paul D. Gilbert,Samantha L. Hider,Anne Hinks,Sally John,Catherine Potter,Alan J. Silman,Deborah P M Symmons,Wendy Thomson,Jane Worthington,David B. Dunger,Barry Widmer,Timothy M. Frayling,Rachel M. Freathy,Hana Lango,John R. B. Perry,Beverley M. Shields,Michael N. Weedon,Andrew T. Hattersley,Graham A. Hitman,Mark Walker,Kate S. Elliott,Christopher J. Groves,Cecilia M. Lindgren,Nigel W. Rayner,Nicholas J. Timpson,Eleftheria Zeggini,Melanie J. Newport,Giorgio Sirugo,Emily J. Lyons,Fredrik O. Vannberg,Adrian V. S. Hill,Linda A. Bradbury,C Farrar,J J Pointon,Paul Wordsworth,Matthew A. Brown,Jayne A. Franklyn,Joanne M. Heward,Matthew J. Simmonds,Stephen C. L. Gough,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Maria Ban,An Goris,Stephen Sawcer,Alastair Compston,David J. Conway,Muminatou Jallow,Kirk A. Rockett,Suzannah Bumpstead,Amy Chaney,Kate Downes,Mohammed J. R. Ghori,Rhian Gwilliam,Sarah E. Hunt,Michael Inouye,Andrew Keniry,Emma King,Ralph McGinnis,Simon C. Potter,Rathi Ravindrarajah,Pamela Whittaker,Claire Widden,David Withers,Niall Cardin,Teresa Ferreira,Joanne Pereira-Gale,Ingileif B. Hallgrímsdóttir,Bryan Howie,Zhan Su,Yik Ying Teo,Damjan Vukcevic,David Bentley,A Compston +195 more
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal ArticleDOI
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Related Papers (5)
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
α-Synuclein Locus Triplication Causes Parkinson's Disease
Andrew B. Singleton,Matthew J. Farrer,Joshua C. Johnson,Amanda Singleton,Stephen Hague,Jennifer M. Kachergus,Mary M. Hulihan,Terhi Peuralinna,Amalia Dutra,Robert L. Nussbaum,Sarah Lincoln,Anthony Crawley,Melissa Hanson,Demetrius M. Maraganore,Charles H. Adler,Mark R. Cookson,Manfred D. Muenter,Melisa J. Baptista,David Miller,J. Blancato,John Hardy,Katrina Gwinn-Hardy +21 more
Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology
Alexander Zimprich,Alexander Zimprich,Saskia Biskup,Petra Leitner,Peter Lichtner,Matthew J. Farrer,Sarah Lincoln,Jennifer M. Kachergus,Mary M. Hulihan,Ryan J. Uitti,Donald B. Calne,A. Jon Stoessl,Ronald F. Pfeiffer,Nadja Patenge,Iria Carballo Carbajal,Peter Vieregge,Friedrich Asmus,Bertram Müller-Myhsok,Dennis W. Dickson,Thomas Meitinger,Tim M. Strom,Zbigniew K. Wszolek,Thomas Gasser +22 more
Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease
Coro Paisán-Ruiz,Shushant Jain,E. Whitney Evans,William P. Gilks,Javier Fernandez de Simon,Marcel P. van der Brug,Adolfo López de Munain,Silvia Aparicio,Angel Martı́nez Gil,Naheed L. Khan,Janel O. Johnson,Javier Ruiz Martínez,David Nicholl,Itxaso Marti Carrera,Amets Saénz Peňa,Rohan de Silva,Andrew J. Lees,Jose Felix Marti-Masso,Jordi Pérez-Tur,Nicholas W. Wood,Andrew B. Singleton +20 more