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

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

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2039-2044
Number of pages6
JournalMovement Disorders
Volume26
Issue number11
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Keywords

  • Leucine-rich repeat kinase 2
  • Linkage
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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    Latourelle, J. C., Hendricks, A. E., Pankratz, N., Wilk, J. B., Halter, C., Nichols, W. C., Gusella, J. F., Destefano, A. L., Myers, R. H., & Foroud, T. (2011). Genomewide linkage study of modifiers of LRRK2-related Parkinson's disease. Movement Disorders, 26(11), 2039-2044. https://doi.org/10.1002/mds.23781