Genetic risk for psychiatric disorders is associated with psychiatric and cognitive huntington's disease symptoms

Background Huntington’s disease (HD) is marked by a progressive movement disorder together with cognitive and psychiatric abnormalities. Psychiatric symptoms are especially difficult for patients and their families, but despite their importance, the molecular understanding of these symptoms is limited. Aims Using polygenic risk scores (PRS), we tested how the risk for certain neuropsychiatric traits were associated with phenotypes seen in HD patients, to better understand genetic mechanisms governing HD symptoms. Methods PRS were calculated for 5,159 HD participants taken from the Enroll and Registry studies, across 11 neuropsychiatric traits. These included risk scores for schizophrenia, obsessive compulsive disorder, suicidality, and intelligence. 45 phenotypes were examined across motor, cognitive and psychiatric domains. Generalised linear models were constructed using the most recent visit data, covarying for HTT CAG size, patient age and approximate disease duration. Results Intelligence PRS were found to be associated with a number of cognitive and functional measures such as total functional capacity (TFC) and the composite Unified Huntington’s Disease Rating Scale (cUHDRS). Obsessive compulsive disorder PRS were associated with dystonia and other motor phenotypes from the total motor score (TMS). Schizophrenia PRS were associated with delusions as reported by the short form problem behaviours assessment (PBA-s), as well as psychosis from the clinical characteristics questionnaire (CCQ). Conclusion Genes underlying neuropsychiatric phenotypes associate with symptoms experienced by HD patients – studying the mechanisms of these manifestations will improve our understanding of Huntington’s disease.