genome wide assessment of young onset parkinson’s disease from finland基因组范围的评估来自芬兰的年轻帕金森病发作.pdfVIP

Genome Wide Assessment of Young Onset Parkinson’s Disease from Finland 1 1 2 1 3 4 Dena G. Hernandez , Michael A. Nalls , Pauli Ylikotila , Margaux Keller , John A. Hardy , Kari Majamaa , Andrew B. Singleton1* 1 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Department of Neurology, Turku University Hospital, Turku, Finland, 3 Reta Lilla Weston Laboratories and Departments of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom, 4 Institute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland Abstract In the current study we undertook a series of experiments to test the hypothesis that a monogenic cause of disease may be detectable within a cohort of Finnish young onset Parkinson’s disease patients. In the first instance we performed standard genome wide association analyses, and subsequent risk profile analysis. In addition we performed a series of analyses that involved testing measures of global relatedness within the cases compared to controls, searching for excess homozygosity in the cases, and examining the cases for signs of excess local genomic relatedness using a sliding window approach. This work suggested that the previously identified common, low risk alleles, and the risk models associated with these alleles, were generalizable to the Finnish Parkinson’s disease population. However, we found no evidence that would suggest a single common high penetrance mutation exists in this cohort of young onset patients. Citation: Hernandez DG, Nalls MA, Ylikotila P, Keller M, Hardy JA, et al. (2012) Genome Wide Assessment of Young Onset Parkinson’s Disease from Finland. PLoS ONE 7(7): e41859