Mike A Nalls1, Valentina Escott-Price2, Nigel M Williams2, Steven Lubbe3, Margaux F Keller4, Huw R Morris3, Andrew B Singleton1. 1. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. 2. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales, UK. 3. Department of Clinical Neuroscience, UCL Institute of Neurology, London, England, UK. 4. Merck Research Laboratories, Cambridge, Massachusetts, USA.
Abstract
BACKGROUND: Recent genomewide association study meta-analyses have identified 28 loci associated with risk of Parkinson's disease (PD). We sought to investigate whether these genetic risk factors are associated with PD age at onset. METHODS: Genetic risk scores from these loci were calculated for 6,249 cases. Linear regression tested associations between cumulative genetic risk and PD age at onset. RESULTS: Increasing genetic risk scores were associated with earlier age at onset (beta = -0.10, P = 2.92 × 10(-8) , adjusted r(2) = 0.27). Single standard deviation increase in genetic risk score is associated with 37.44 d earlier age at onset. Highest genetic risk was found at 31 to 60 y, onset slightly below average age at onset (AAO). CONCLUSIONS: Common genetic risk factors have a small but consistent association with AAO in PD.
BACKGROUND: Recent genomewide association study meta-analyses have identified 28 loci associated with risk of Parkinson's disease (PD). We sought to investigate whether these genetic risk factors are associated with PD age at onset. METHODS: Genetic risk scores from these loci were calculated for 6,249 cases. Linear regression tested associations between cumulative genetic risk and PD age at onset. RESULTS: Increasing genetic risk scores were associated with earlier age at onset (beta = -0.10, P = 2.92 × 10(-8) , adjusted r(2) = 0.27). Single standard deviation increase in genetic risk score is associated with 37.44 d earlier age at onset. Highest genetic risk was found at 31 to 60 y, onset slightly below average age at onset (AAO). CONCLUSIONS: Common genetic risk factors have a small but consistent association with AAO in PD.
Authors: Samuli Ripatti; Emmi Tikkanen; Marju Orho-Melander; Aki S Havulinna; Kaisa Silander; Amitabh Sharma; Candace Guiducci; Markus Perola; Antti Jula; Juha Sinisalo; Marja-Liisa Lokki; Markku S Nieminen; Olle Melander; Veikko Salomaa; Leena Peltonen; Sekar Kathiresan Journal: Lancet Date: 2010-10-23 Impact factor: 79.321
Authors: Adriano Chiò; Jennifer C Schymick; Gabriella Restagno; Sonja W Scholz; Federica Lombardo; Shiao-Lin Lai; Gabriele Mora; Hon-Chung Fung; Angela Britton; Sampath Arepalli; J Raphael Gibbs; Michael Nalls; Stephen Berger; Lydia Coulter Kwee; Eugene Z Oddone; Jinhui Ding; Cynthia Crews; Ian Rafferty; Nicole Washecka; Dena Hernandez; Luigi Ferrucci; Stefania Bandinelli; Jack Guralnik; Fabio Macciardi; Federica Torri; Sara Lupoli; Stephen J Chanock; Gilles Thomas; David J Hunter; Christian Gieger; H Erich Wichmann; Andrea Calvo; Roberto Mutani; Stefania Battistini; Fabio Giannini; Claudia Caponnetto; Giovanni Luigi Mancardi; Vincenzo La Bella; Francesca Valentino; Maria Rosaria Monsurrò; Gioacchino Tedeschi; Kalliopi Marinou; Mario Sabatelli; Amelia Conte; Jessica Mandrioli; Patrizia Sola; Fabrizio Salvi; Ilaria Bartolomei; Gabriele Siciliano; Cecilia Carlesi; Richard W Orrell; Kevin Talbot; Zachary Simmons; James Connor; Erik P Pioro; Travis Dunkley; Dietrich A Stephan; Dalia Kasperaviciute; Elizabeth M Fisher; Sibylle Jabonka; Michael Sendtner; Marcus Beck; Lucie Bruijn; Jeffrey Rothstein; Silke Schmidt; Andrew Singleton; John Hardy; Bryan J Traynor Journal: Hum Mol Genet Date: 2009-02-04 Impact factor: 6.150
Authors: Michael A Nalls; Vincent Plagnol; Dena G Hernandez; Manu Sharma; Una-Marie Sheerin; Mohamad Saad; J Simón-Sánchez; Claudia Schulte; Suzanne Lesage; Sigurlaug Sveinbjörnsdóttir; Kári Stefánsson; Maria Martinez; John Hardy; Peter Heutink; Alexis Brice; Thomas Gasser; Andrew B Singleton; Nicholas W Wood Journal: Lancet Date: 2011-02-01 Impact factor: 79.321
Authors: Christina M Lill; Johannes T Roehr; Matthew B McQueen; Fotini K Kavvoura; Sachin Bagade; Brit-Maren M Schjeide; Leif M Schjeide; Esther Meissner; Ute Zauft; Nicole C Allen; Tian Liu; Marcel Schilling; Kari J Anderson; Gary Beecham; Daniela Berg; Joanna M Biernacka; Alexis Brice; Anita L DeStefano; Chuong B Do; Nicholas Eriksson; Stewart A Factor; Matthew J Farrer; Tatiana Foroud; Thomas Gasser; Taye Hamza; John A Hardy; Peter Heutink; Erin M Hill-Burns; Christine Klein; Jeanne C Latourelle; Demetrius M Maraganore; Eden R Martin; Maria Martinez; Richard H Myers; Michael A Nalls; Nathan Pankratz; Haydeh Payami; Wataru Satake; William K Scott; Manu Sharma; Andrew B Singleton; Kari Stefansson; Tatsushi Toda; Joyce Y Tung; Jeffery Vance; Nick W Wood; Cyrus P Zabetian; Peter Young; Rudolph E Tanzi; Muin J Khoury; Frauke Zipp; Hans Lehrach; John P A Ioannidis; Lars Bertram Journal: PLoS Genet Date: 2012-03-15 Impact factor: 5.917
Authors: Javier Simón-Sánchez; Claudia Schulte; Jose M Bras; Manu Sharma; J Raphael Gibbs; Daniela Berg; Coro Paisan-Ruiz; Peter Lichtner; Sonja W Scholz; Dena G Hernandez; Rejko Krüger; Monica Federoff; Christine Klein; Alison Goate; Joel Perlmutter; Michael Bonin; Michael 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 Zonozi; Katrina Gwinn; Marcel van der Brug; Grisel Lopez; Stephen J Chanock; Arthur Schatzkin; Yikyung Park; Albert Hollenbeck; Jianjun Gao; Xuemei Huang; Nick W Wood; Delia Lorenz; Günther Deuschl; Honglei Chen; Olaf Riess; John A Hardy; Andrew B Singleton; Thomas Gasser Journal: Nat Genet Date: 2009-11-15 Impact factor: 38.330
Authors: Dena G Hernandez; Michael A Nalls; Pauli Ylikotila; Margaux Keller; John A Hardy; Kari Majamaa; Andrew B Singleton Journal: PLoS One Date: 2012-07-24 Impact factor: 3.240
Authors: Laura L Kilarski; Justin P Pearson; Victoria Newsway; Elisa Majounie; M Duleeka W Knipe; Anjum Misbahuddin; Patrick F Chinnery; David J Burn; Carl E Clarke; Marie-Helene Marion; Alistair J Lewthwaite; David J Nicholl; Nicholas W Wood; Karen E Morrison; Caroline H Williams-Gray; Jonathan R Evans; Stephen J Sawcer; Roger A Barker; Mirdhu M Wickremaratchi; Yoav Ben-Shlomo; Nigel M Williams; Huw R Morris Journal: Mov Disord Date: 2012-09-06 Impact factor: 10.338
Authors: Sara Bandrés-Ciga; Timothy Ryan Price; Francisco Javier Barrero; Francisco Escamilla-Sevilla; Javier Pelegrina; Sampath Arepalli; Dena Hernández; Blanca Gutiérrez; Jorge Cervilla; Margarita Rivera; Alberto Rivera; Jing-Hui Ding; Francisco Vives; Michael Nalls; Andrew Singleton; Raquel Durán Journal: Neurobiol Aging Date: 2016-06-11 Impact factor: 4.673
Authors: J A Obeso; M Stamelou; C G Goetz; W Poewe; A E Lang; D Weintraub; D Burn; G M Halliday; E Bezard; S Przedborski; S Lehericy; D J Brooks; J C Rothwell; M Hallett; M R DeLong; C Marras; C M Tanner; G W Ross; J W Langston; C Klein; V Bonifati; J Jankovic; A M Lozano; G Deuschl; H Bergman; E Tolosa; M Rodriguez-Violante; S Fahn; R B Postuma; D Berg; K Marek; D G Standaert; D J Surmeier; C W Olanow; J H Kordower; P Calabresi; A H V Schapira; A J Stoessl Journal: Mov Disord Date: 2017-09 Impact factor: 10.338
Authors: Lauren A Dalvin; Gena M Damento; Barbara P Yawn; Barbara A Abbott; David O Hodge; Jose S Pulido Journal: Mayo Clin Proc Date: 2017-07 Impact factor: 7.616
Authors: Victoria Berge-Seidl; Lasse Pihlstrøm; Zbigniew K Wszolek; Owen A Ross; Mathias Toft Journal: Neurobiol Aging Date: 2018-09-22 Impact factor: 4.673