BACKGROUND: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. METHODS: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. RESULTS: Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10(-4); rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10(-4)). CONCLUSIONS: Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry.
BACKGROUND: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. METHODS: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PDpatients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. RESULTS: Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10(-4); rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10(-4)). CONCLUSIONS: Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry.
Authors: C P Zabetian; A Samii; A D Mosley; J W Roberts; B C Leis; D Yearout; W H Raskind; A Griffith Journal: Neurology Date: 2005-09-13 Impact factor: 9.910
Authors: Saskia Biskup; Jakob C Mueller; Manu Sharma; Peter Lichtner; Alexander Zimprich; Daniela Berg; Ullrich Wüllner; Thomas Illig; Thomas Meitinger; Thomas Gasser Journal: Ann Neurol Date: 2005-12 Impact factor: 10.422
Authors: Gail A Kang; Jeff M Bronstein; Donna L Masterman; Matthew Redelings; Jarrod A Crum; Beate Ritz Journal: Mov Disord Date: 2005-09 Impact factor: 10.338
Authors: Harvey Checkoway; Karen Powers; Terri Smith-Weller; Gary M Franklin; W T Longstreth; Phillip D Swanson Journal: Am J Epidemiol Date: 2002-04-15 Impact factor: 4.897
Authors: Cyrus P Zabetian; Mitsutoshi Yamamoto; Alexis N Lopez; Hiroshi Ujike; Ignacio F Mata; Yuishin Izumi; Ryuji Kaji; Hirofumi Maruyama; Hiroyuki Morino; Masaya Oda; Carolyn M Hutter; Karen L Edwards; Gerard D Schellenberg; Debby W Tsuang; Dora Yearout; Eric B Larson; Hideshi Kawakami Journal: Mov Disord Date: 2009-05-15 Impact factor: 10.338
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: Asha Kishore; Ashwin Ashok Kumar Sreelatha; Marc Sturm; Felix von-Zweydorf; Lasse Pihlstrøm; Francesco Raimondi; Rob Russell; Peter Lichtner; Moinak Banerjee; Syam Krishnan; Roopa Rajan; Divya Kalikavil Puthenveedu; Sun Ju Chung; Peter Bauer; Olaf Riess; Christian Johannes Gloeckner; Rejko Kruger; Thomas Gasser; Manu Sharma Journal: Mov Disord Date: 2018-11-28 Impact factor: 10.338
Authors: Carla Ribeiro Alvares Batista; Giovanni Freitas Gomes; Eduardo Candelario-Jalil; Bernd L Fiebich; Antonio Carlos Pinheiro de Oliveira Journal: Int J Mol Sci Date: 2019-05-09 Impact factor: 5.923
Authors: Kenneth Thirstrup; Justus C Dächsel; Felix S Oppermann; Douglas S Williamson; Garrick P Smith; Karina Fog; Kenneth V Christensen Journal: Sci Rep Date: 2017-08-31 Impact factor: 4.379
Authors: Emmeline E Brown; Cornelis Blauwendraat; Joanne Trinh; Mie Rizig; Mike A Nalls; Etienne Leveille; Jennifer A Ruskey; Hallgeir Jonvik; Manuela M X Tan; Sara Bandres-Ciga; Sharon Hassin-Baer; Kathrin Brockmann; Jon Infante; Eduardo Tolosa; Mario Ezquerra; Sawssan Ben Romdhan; Mustapha Benmahdjoub; Mohamed Arezki; Chokri Mhiri; John Hardy; Andrew B Singleton; Roy N Alcalay; Thomas Gasser; Donald G Grosset; Nigel M Williams; Alan Pittman; Ziv Gan-Or; Ruben Fernandez-Santiago; Alexis Brice; Suzanne Lesage; Matthew Farrer; Nicholas Wood; Huw R Morris Journal: Neurobiol Aging Date: 2020-07-13 Impact factor: 4.673