These authors contributed equally to this manuscript.
C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease
Article first published online: 12 JUL 2013
© 2013 The Authors. Annals of Human Genetics published by John Wiley & Sons Ltd/University College London
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Annals of Human Genetics
Volume 77, Issue 5, pages 351–363, September 2013
How to Cite
Nuytemans, K., Bademci, G., Kohli, M. M., Beecham, G. W., Wang, L., Young, J. I., Nahab, F., Martin, E. R., Gilbert, J. R., Benatar, M., Haines, J. L., Scott, W. K., Züchner, S., Pericak-Vance, M. A. and Vance, J. M. (2013), C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease. Annals of Human Genetics, 77: 351–363. doi: 10.1111/ahg.12033
- Issue published online: 6 AUG 2013
- Article first published online: 12 JUL 2013
- Manuscript Accepted: 4 JUN 2013
- Manuscript Received: 7 NOV 2012
- National Institute of Health. Grant Numbers: NS39764, 5P50NS071674-03, R01AG019085, R01AG027944-02, R01AG028786-02, RC2AG036528, U01AG032984-02
- Alzheimer's Association
- American Health Assistance Foundation
- Parkinson disease;
- C9ORF72 repeat;
- risk factor
We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat-primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002). Further, seven cases and no controls had >23 repeat copies (p = 0.003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP. This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders.