Genetic Risk Underlying Psychiatric and Cognitive Symptoms in Huntington’s Disease

Natalie Ellis; Amelia Tee; Branduff McAllister; Thomas Massey; Duncan McLauchlan; Timothy Stone; Kevin Correia; Jacob Loupe; Kyung-Hee Kim; Douglas Barker; Eun Pyo Hong; Michael J Chao; Jeffrey D Long; Diane Lucente; Jean Paul G Vonsattel; Ricardo Mouro Pinto; Kawther Abu Elneel; Eliana Marisa Ramos; Jayalakshmi Srinidhi Mysore; Tammy Gillis; Vanessa C Wheeler; Christopher Medway; Lynsey Hall; Seung Kwak; Cristina Sampaio; Marc Ciosi; Alastair Maxwell; Afroditi Chatzi; Darren G Monckton; Michael Orth; G. Bernhard Landwehrmeyer; Jane S Paulsen; Ira Shoulson; Richard H Myers; Erik van Duijn; Hugh Rickards; Marcy E MacDonald; Jong-min Lee; James F Gusella; Lesley Jones; Peter Holmans

doi:10.1016/j.biopsych.2019.12.010

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Genetic Risk Underlying Psychiatric and Cognitive Symptoms in Huntington’s Disease

Journal article

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Genetic Risk Underlying Psychiatric and Cognitive Symptoms in Huntington’s Disease

Natalie Ellis, Amelia Tee, Branduff McAllister, Thomas Massey, Duncan McLauchlan, Timothy Stone, Kevin Correia, Jacob Loupe, Kyung-Hee Kim, Douglas Barker, …

Biological psychiatry (1969), Vol.87(9), pp.857-865

05/01/2020

DOI: 10.1016/j.biopsych.2019.12.010

PMCID: PMC7156911

PMID: 32087949

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Abstract

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 examination 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. 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. 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. 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.

Cognition

Depression

Huntington’s disease

Polygenic risk

Psychiatric

Schizophrenia

Details

Title: Subtitle: Genetic Risk Underlying Psychiatric and Cognitive Symptoms in Huntington’s Disease
Creators: Natalie Ellis - Cardiff University
Amelia Tee - Cardiff University
Branduff McAllister - Cardiff University
Thomas Massey - Cardiff University
Duncan McLauchlan - Cardiff University
Timothy Stone - University College London
Kevin Correia - Massachusetts General Hospital
Jacob Loupe - HudsonAlpha Institute for Biotechnology
Kyung-Hee Kim - Massachusetts General Hospital
Douglas Barker - Massachusetts General Hospital
Eun Pyo Hong - Massachusetts General Hospital
Michael J Chao - Massachusetts General Hospital
Jeffrey D Long - University of Iowa
Diane Lucente - Massachusetts General Hospital
Jean Paul G Vonsattel - Columbia University Irving Medical Center
Ricardo Mouro Pinto - Massachusetts General Hospital
Kawther Abu Elneel - Massachusetts General Hospital
Eliana Marisa Ramos - Massachusetts General Hospital
Jayalakshmi Srinidhi Mysore - Massachusetts General Hospital
Tammy Gillis - Massachusetts General Hospital
Vanessa C Wheeler - Massachusetts General Hospital
Christopher Medway - University Hospital of Wales
Lynsey Hall - Cardiff University
Seung Kwak - CHDI Foundation
Cristina Sampaio - CHDI Foundation
Marc Ciosi - University of Glasgow
Alastair Maxwell - University of Glasgow
Afroditi Chatzi - University of Glasgow
Darren G Monckton - University of Glasgow
Michael Orth - Universität Ulm
G. Bernhard Landwehrmeyer - Universität Ulm
Jane S Paulsen - University of Iowa
Ira Shoulson - University of Rochester Medical Center
Richard H Myers - Boston University
Erik van Duijn - Leiden University Medical Center
Hugh Rickards - University of Birmingham
Marcy E MacDonald - Massachusetts General Hospital
Jong-min Lee - Massachusetts General Hospital
James F Gusella - Massachusetts General Hospital
Lesley Jones - Cardiff University
Peter Holmans - Cardiff University
Resource Type: Journal article
Publication Details: Biological psychiatry (1969), Vol.87(9), pp.857-865
DOI: 10.1016/j.biopsych.2019.12.010
PMID: 32087949
PMCID: PMC7156911
NLM abbreviation: Biol Psychiatry
ISSN: 0006-3223
eISSN: 1873-2402
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100005725, name: CHDI Foundation; DOI: 10.13039/100000002, name: National Institutes of Health, award: U01NS082079 [to JFG, R01NS040068 [to JSP, R01NS091161 [to JFG, P50NS016367 [to JFG, R01NS049206 [to VCW; DOI: 10.13039/501100000265, name: Medical Research Council, award: MR/L010305/1 [to LJ, PH
Language: English
Date published: 05/01/2020
Academic Unit: Psychiatry; Psychological and Brain Sciences; Biostatistics
Record Identifier: 9984280833802771

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