Common variants in PARK loci and related genes and Parkinson's disease

Sun Ju Chung, Sebastian M. Armasu, Joanna M. Biernacka, Timothy G. Lesnick, David N. Rider, Sarah J. Lincoln, Alexandra I. Ortolaza, Matthew J. Farrer, Julie M. Cunningham, Walter A. Rocca, Demetrius M. Maraganore

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25 Scopus citations

Abstract

Rare mutations in PARK loci genes cause Parkinson's disease (PD) in some families and isolated populations. We investigated the association of common variants in PARK loci and related genes with PD susceptibility and age at onset in an outbred population. A total of 1,103 PD cases from the upper Midwest, USA, were individually matched to unaffected siblings (n = 654) or unrelated controls (n = 449) from the same region. Using a sequencing approach in 25 cases and 25 controls, single nucleotide polymorphisms (SNPs) in species-conserved regions of PARK loci and related genes were detected. We selected additional tag SNPs from the HapMap. We genotyped a total of 235 SNPs and two variable number tandem repeats in the ATP13A2, DJ1, LRRK1, LRRK2, MAPT, Omi/HtrA2, PARK2, PINK1, SNCA, SNCB, SNCG, SPR, and UCHL1 genes in all 2,206 subjects. Case-control analyses were performed to study association with PD susceptibility, while cases-only analyses were used to study association with age at onset. Only MAPT SNP rs2435200 was associated with PD susceptibility after correction for multiple testing (OR = 0.74, 95% CI = 0.64-0.86, uncorrected P < 0.0001, log additive model); however, 16 additional MAPT variants, seven SNCA variants, and one LRRK2, PARK2, and UCHL1 variants each had significant uncorrected P-values. There were no significant associations for age at onset after correction for multiple testing. Our results confirm the association of MAPT and SNCA genes with PD susceptibility but show limited association of other PARK loci and related genes with PD.

Original languageEnglish (US)
Pages (from-to)280-288
Number of pages9
JournalMovement Disorders
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2011

Keywords

  • Age at onset of parkinson's disease
  • Common genetic variants
  • PARK loci genes
  • Parkinson's disease
  • Susceptibility to parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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  • Cite this

    Chung, S. J., Armasu, S. M., Biernacka, J. M., Lesnick, T. G., Rider, D. N., Lincoln, S. J., Ortolaza, A. I., Farrer, M. J., Cunningham, J. M., Rocca, W. A., & Maraganore, D. M. (2011). Common variants in PARK loci and related genes and Parkinson's disease. Movement Disorders, 26(2), 280-288. https://doi.org/10.1002/mds.23376