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- Title
High and Low Levels of an NTRK2-Driven Genetic Profile Affect Motor- and Cognition-Associated Frontal Gray Matter in Prodromal Huntington’s Disease.
- Authors
Ciarochi, Jennifer A.; Turner, Jessica A.; Liu, Jingyu; Bockholt, H. Jeremy; Espinoza, Flor A.; Caprihan, Arvind; Plis, Sergey; Calhoun, Vince; Johnson, Hans; Paulsen, Jane S.; Misiura, Maria
- Abstract
This study assessed how <italic>BDNF</italic> (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 (<italic>N</italic> = 715). pICA identified a genetic component highlighting <italic>NTRK2</italic>, which encodes BDNF’s TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (<italic>p</italic> < 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 (<italic>p</italic> = 0.03); Stroop Color (<italic>p</italic> = 0.017); Stroop Interference (<italic>p</italic> = 0.04); Symbol Digit Modalities Test (<italic>p</italic> = 0.031); Total Motor Score (<italic>p</italic> = 0.01)). A top-weighted <italic>NTRK2</italic> variant (rs2277193) was protectively associated with Trail Making Test B (<italic>p</italic> = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of <italic>NTRK2</italic> 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.
- Subjects
BRAIN-derived neurotrophic factor; GENES; HUNTINGTON disease; GRAY matter (Nerve tissue); PREMOTOR cortex; GENOTYPES; GENETIC profile
- Publication
Brain Sciences (2076-3425), 2018, Vol 8, Issue 7, p116
- ISSN
2076-3425
- Publication type
Article
- DOI
10.3390/brainsci8070116