Year: 2011
Type: article
Study design: Observational Study
Abstract: Mutations in the leucine-rich repeat kinase 2 gene, located at 12q12, are the most common known genetic causes of Parkinson's disease. Studies of leucine-rich repeat kinase 2 mutation carriers have shown incomplete and age-dependent penetrance, and previous studies have suggested that inherited susceptibility factors may modify the penetrance of leucine-rich repeat kinase 2 mutations. Genomewide linkage to age of onset of leucine-rich repeat kinase 2-related Parkinson's disease was evaluated in a sample of 113 leucine-rich repeat kinase 2 mutation carriers from 64 families using single-nucleotide polymorphism data from the Illumina HumanCNV370 genotyping array. Association between onset age and single-nucleotide polymorphisms under suggestive linkage peaks was also evaluated. The top logarithmic odds score for onset age (logarithmic odds score = 2.43) was in the chromosome 1q32.1 region. Moderate linkage to onset was also identified at 16q12.1 (logarithmic odds score = 1.58). Examination of single-nucleotide polymorphism association to Parkinson's disease onset under the linkage peaks revealed no statistically significant single-nucleotide polymorphism associations. The 2 novel genomic regions identified may harbor modifiers of leucine-rich repeat kinase 2-related Parkinson's disease onset age or penetrance, and further study of these regions may provide important insight into leucine-rich repeat kinase 2-related Parkinson's disease.
Source: Movement Disorders
DOI: 10.1002/mds.23781
Authors: Jeanne C. Latourelle, Audrey E. Hendricks, Nathan Pankratz, Jemma B. Wilk, Cheryl Halter, William C. Nichols, James F. Gusella, Anita L. Destefano, Richard H. Myers, Tatiana Foroud, and the PSG–Progeni GenePD Investigators, Coordinators, and Molecular Genetic Laboratories
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Harvard NeuroDiscovery Center, Eli Lilly and Company, Massachusetts General Hospital, Brown University, Northwestern University, Creighton University, School of Medicine, Boston University, Cleveland Clinic, Johns Hopkins University, University of Rochester, Fondazione Grigioni per il Morbo di Parkinson, National Institutes of Health, Health Science Center, University of Tennessee, University of California, Irvine, School of Medicine, Indiana University, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W2040105433