Allison A. Dilliott, Institut-Hôpital Neurologique de Montréal
Kristina K. Zhang, Schulich School of Medicine & Dentistry
Jian Wang, Robarts Research Institute
Agessandro Abrahao, University of Toronto
Malcolm A. Binns, Rotman Research Institute
Sandra E. Black, University of Toronto
Michael Borrie, St. Joseph's Health Care London
Dar Dowlatshahi, L'Hôpital d'Ottawa
Elizabeth Finger, Schulich School of Medicine & DentistryFollow
Corinne E. Fischer, Keenan Research Centre for Biomedical Science
Andrew Frank, L'Hôpital d'Ottawa
Morris Freedman, Rotman Research Institute
David Grimes, L'Hôpital d'Ottawa
Ayman Hassan, École de médecine du Nord de l'Ontario
Mandar Jog, Schulich School of Medicine & Dentistry
Sanjeev Kumar, Centre for Addiction and Mental Health
Anthony E. Lang, Toronto Western Hospital University of Toronto
Jennifer Mandzia, Schulich School of Medicine & Dentistry
Mario Masellis, University of Toronto
Stephen H. Pasternak, Robarts Research InstituteFollow
Bruce G. Pollock, Centre for Addiction and Mental Health
Tarek K. Rajji, Centre for Addiction and Mental Health
Ekaterina Rogaeva, Tanz Centre for Research in Neurodegenerative Diseases
Demetrios J. Sahlas, McMaster University
Gustavo Saposnik, Li Ka Shing Knowledge Institute
Christine Sato, Tanz Centre for Research in Neurodegenerative Diseases
Dallas Seitz, Cumming School of Medicine
Christen Shoesmith, London Health Sciences Centre
Thomas D.L. Steeves, Schulich School of Medicine & Dentistry
Richard H. Swartz, University of Toronto

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Molecular Genetics and Genomic Medicine





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Background: Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied. Methods: Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519). Results: In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in OPTN in an Alzheimer's disease participant; (2) a duplication of exons 1–5 in PARK7 in an amyotrophic lateral sclerosis participant; (3) a duplication of >3 Mb, which encompassed ABCC6, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7–11 in SAMHD1 in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies. Conclusion: The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration.