Genetic risk underlying psychiatric and cognitive symptoms in Huntington’s Disease

Ellis, N. et al. (2020) Genetic risk underlying psychiatric and cognitive symptoms in Huntington’s Disease. Biological Psychiatry, 87(9), pp. 857-865. (doi: 10.1016/j.biopsych.2019.12.010) (PMID:32087949)

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Background: Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized exam of motor control and often presents with cognitive decline and psychiatric symptoms. Recent studies have detected genetic loci modifying the age at onset of motor symptoms in HD, but genetic factors influencing cognitive and psychiatric presentations are unknown. Methods: We tested the hypothesis that psychiatric and cognitive symptoms in HD are influenced by the same common genetic variation as in the general population by constructing polygenic risk scores from large genome-wide association studies of psychiatric and neurodegenerative disorders, and of intelligence, and testing for correlation with the presence of psychiatric and cognitive symptoms in a large sample (n=5160) of HD patients. Results: Polygenic risk score for major depression was associated specifically with increased risk of depression in HD, as was schizophrenia risk score with psychosis and irritability. Cognitive impairment and apathy were associated with reduced polygenic risk score for intelligence. Conclusions: Polygenic risk scores for psychiatric disorders, particularly depression and schizophrenia, are associated with increased risk of the corresponding psychiatric symptoms in HD, suggesting a common genetic liability. However, the genetic liability to cognitive impairment and apathy appears to be distinct from other psychiatric symptoms in HD. No associations were observed between HD symptoms and risk scores for other neurodegenerative disorders. These data provide a rationale for treatments effective in depression and schizophrenia to be used to treat depression and psychotic symptoms in HD.

Item Type:Articles
Additional Information:This work was supported by the CHDI Foundation, the National Institutes of Health USA (U01NS082079, R01NS040068, R01NS091161, P50NS016367, and R01NS049206) and the Medical Research Council (UK; MR/L010305/1). Dr. Massey received a fellowship from the MRC (MR/P001629/1) and Mr. McAllister received a studentship from the Cardiff University School of Medicine.
Glasgow Author(s) Enlighten ID:Maxwell, Mr Alastair and Monckton, Professor Darren and Chatzi, Ms Afroditi and Ciosi, Dr Marc
Authors: Ellis, N., Tee, A., McAllister, B., Massey, T., McLauchlan, D., Stone, T., Correia, K., Loupe, J., Kim, K.-H., Barker, D., Hong, E. P., Chao, M. J., Long, J. D., Lucente, D., Vonsattel, J. P. G., Pinto, R. M., Elneel, K. A., Ramos, E. M., Mysore, J. S., Gillis, T., Wheeler, V. C., Medway, C., Hall, L., Kwak, S., Sampaio, C., Ciosi, M., Maxwell, A., Chatzi, A., Monckton, D. G., Orth, M., Landwehrmeyer, G. B., Paulsen, J. S., Shoulson, I., Myers, R. H., van Duijn, E., Rickards, H., MacDonald, M. E., Lee, J.-m., Gusella, J. F., Jones, L., and Holmans, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Biological Psychiatry
ISSN (Online):1873-2402
Published Online:17 December 2019
Copyright Holders:Copyright © 2020 Society of Biological Psychiatry
First Published:First published in Biological Psychiatry 87(9):857-865
Publisher Policy:Reproduced under a Creative Commons License

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