Genomewide linkage study of modifiers of LRRK2-related Parkinson's disease§

Authors


  • Funding agencies: This project was supported by R01 NS37167, R01 NS036711, the Robert P. & Judith N. Goldberg Foundation, the Bumpus Foundation, and the Harvard NeuroDiscovery Center. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine, and Boston Medical Center. Genotyping services were provided by the Center for Inherited Disease Research (CIDR), fully funded through a federal contract from the National Institutes of Health to Johns Hopkins University (contract HHSN268200782096C).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

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. © 2011 Movement Disorder Society

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