Increased rate of sporadic and recurrent rare genic copy number variants in parkinson’s disease among Ashkenazi Jews

Xinmin Liu, Rong Cheng, Xin Ye, Miguel Verbitsky, Sergey Kisselev, Helen Mejia-Santana, Elan D. Louis, Lucien J. Cote, Howard F. Andrews, Cheryl H. Waters, Blair Ford, Stanley Fahn, Karen Marder, Joseph H. Lee, Lorraine N. Clark

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


To date, only one genome-wide study has assessed the contribution of copynumber variants (CNVs) to Parkinson’s disease (PD). We conducted a genome-wide scan for CNVs in a case–control dataset of Ashkenazi Jewish (AJ)origin (268 PD cases and 178 controls). Using high-confidence CNVs, weexamined the global genome wide burden of large (≥100 kb) and rare (≤1% inthe dataset) CNVs between cases and controls. A total of 986 such CNVs wereobserved in our dataset of 432 subjects. Overall global burden analyses did notreveal significant differences between cases and controls in CNV rate, distributionof deletions or duplications or number of genes affected by CNVs. Overalldeletions (total CNV size and ≥29 frequency) were found 1.4 times more oftenin cases than in controls (P = 0.019). The large CNVs (≥500 kb) were alsosignificantly associated with PD (P = 0.046, 1.24-fold higher in cases than incontrols). Global burden was elevated for rare CNV regions. Specifically, forOVOS2 on Chr12p11.21, CNVs were observed only in PD cases (n = 7) butnot in controls (P = 0.028) and this was experimentally validated. A total of 81PD cases carried a rare genic CNV that was absent in controls. Ingenuity pathwayanalysis (IPA) identified ATXN3, FBXW7, CHCHD3, HSF1, KLC1, andMBD3 in the same disease pathway with known PD genes.

Original languageEnglish (US)
Pages (from-to)142-154
Number of pages13
JournalMolecular Genetics and Genomic Medicine
Issue number3
StatePublished - Sep 2013
Externally publishedYes


  • Ashkenazi Jews
  • CNV
  • Candidate genes
  • Case–control study
  • Parkinson’s disease

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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