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High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington's disease

Ciarochi, JA; Liu, J; Calhoun, V; Johnson, H; Misiura, M; Bockholt, HJ; Espinoza, FA; ... McMillan, J; + view all (2018) High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington's disease. Brain Sciences , 8 (7) , Article 116. 10.3390/brainsci8070116. Green open access

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Abstract

This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington’s disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort (N = 715). pICA identified a genetic component highlighting NTRK2, which encodes BDNF’s TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (p < 0.001); this association appeared to be driven by participants with high or low levels of the genetic profile. The frontal GMC profile correlated with cognitive and motor variables (Trail Making Test A (p = 0.03); Stroop Color (p = 0.017); Stroop Interference (p = 0.04); Symbol Digit Modalities Test (p = 0.031); Total Motor Score (p = 0.01)). A top-weighted NTRK2 variant (rs2277193) was protectively associated with Trail Making Test B (p = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of NTRK2 in prodromal HD, particularly in individuals with certain genotypes, and suggest that this gene may influence the preservation of frontal gray matter that is important for clinical functioning.

Type: Article
Title: High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington's disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/brainsci8070116
Publisher version: https://doi.org/10.3390/brainsci8070116
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
Keywords: Huntington’s disease; brain-derived neurotrophic factor; tropomyosin receptor kinase B; supplementary motor; independent component analysis
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10053985
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