BACKGROUND: 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. METHODS: The Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. RESULTS: Herein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. CONCLUSIONS: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.
BACKGROUND: 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. METHODS: The Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. RESULTS: Herein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. CONCLUSIONS: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.
Authors: A B Singleton; M Farrer; J Johnson; A Singleton; S Hague; J Kachergus; M Hulihan; T Peuralinna; A Dutra; R Nussbaum; S Lincoln; A Crawley; M Hanson; D Maraganore; C Adler; M R Cookson; M Muenter; M Baptista; D Miller; J Blancato; J Hardy; K Gwinn-Hardy Journal: Science Date: 2003-10-31 Impact factor: 47.728
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Authors: Youren Tong; Hiroo Yamaguchi; Emilie Giaime; Scott Boyle; Raphael Kopan; Raymond J Kelleher; Jie Shen Journal: Proc Natl Acad Sci U S A Date: 2010-05-10 Impact factor: 11.205
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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
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