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

Jennifer A. Ciarochi, Jingyu Liu, Vince Calhoun, Hans J. Johnson, Maria Misiura, H. Jeremy Bockholt, Flor A. Espinoza, Arvind Caprihan, Sergey Plis, Jessica A. Turner, Jane S. Paulsen, PREDICT-HD Investigators and Coordinators of the Huntington

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2 Citations (Scopus)


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.

Original languageEnglish
Article number116
Number of pages24
JournalBrain Sciences
Issue number7
Publication statusPublished - Jul 2018
Externally publishedYes


  • Brain-derived neurotrophic factor
  • Huntington’s disease
  • Independent component analysis
  • Supplementary motor
  • Tropomyosin receptor kinase B

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