Genetic Risk Underlying Psychiatric and Cognitive Symptoms in Huntington's Disease.
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Ellis Natalie, Tee Amelia, McAllister Branduff, Massey Thomas, McLauchlan Duncan, Stone Timothy, Correia Kevin, Loupe Jacob, Kim Kyung-Hee, Barker Douglas, Hong Eun Pyo, Chao Michael J, Long Jeffrey D, Lucente Diane, Vonsattel Jean Paul G, Pinto Ricardo Mouro, Elneel Kawther Abu, Ramos Eliana Marisa, Mysore Jayalakshmi Srinidhi, Gillis Tammy, Wheeler Vanessa C, Medway Christopher, Hall Lynsey, Kwak Seung, Sampaio Cristina, Ciosi Marc, Maxwell Alastair, Chatzi Afroditi, Monckton Darren G, Orth Michael, Landwehrmeyer G Bernhard, Paulsen Jane S, Shoulson Ira, Myers Richard H, van Duijn Erik, Rickards Hugh, MacDonald Marcy E, Lee Jong-Min, Gusella James F, Jones Lesley, Holmans Peter
Аннотация
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 1) constructing polygenic risk scores from large genome-wide association studies of psychiatric and neurodegenerative disorders and of intelligence and 2) testing for correlation with the presence of psychiatric and cognitive symptoms in a large sample (n = 5160) of patients with HD.
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.