Genomic determinants of motor and cognitive outcomes in Parkinson's disease

Sun Ju Chung, Sebastian M. Armasu, Joanna M. Biernacka, Kari J. Anderson, Timothy G. Lesnick, David N. Rider, Julie M. Cunningham, J. Eric Ahlskog, Roberta Frigerio, Demetrius M. Maraganore

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background: Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD). Objective: To identify common genetic variants associated with motor and cognitive outcomes in PD. Methods: The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes). Results: The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10-6). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10-6). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD. Conclusions: This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility.

Original languageEnglish (US)
Pages (from-to)881-886
Number of pages6
JournalParkinsonism and Related Disorders
Volume18
Issue number7
DOIs
StatePublished - Aug 2012

Keywords

  • Genome-wide association studies
  • Outcomes
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

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  • Cite this

    Chung, S. J., Armasu, S. M., Biernacka, J. M., Anderson, K. J., Lesnick, T. G., Rider, D. N., Cunningham, J. M., Eric Ahlskog, J., Frigerio, R., & Maraganore, D. M. (2012). Genomic determinants of motor and cognitive outcomes in Parkinson's disease. Parkinsonism and Related Disorders, 18(7), 881-886. https://doi.org/10.1016/j.parkreldis.2012.04.025