TY - JOUR
T1 - High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington’s disease
AU - PREDICT-HD Investigators and Coordinators of the Huntington
AU - Ciarochi, Jennifer A.
AU - Liu, Jingyu
AU - Calhoun, Vince
AU - Johnson, Hans
AU - Misiura, Maria
AU - Bockholt, H. Jeremy
AU - Espinoza, Flor A.
AU - Caprihan, Arvind
AU - Plis, Sergey
AU - Turner, Jessica A.
AU - Paulsen, Jane S.
AU - Long, Jeffrey D.
AU - Brashers-Krug, Thomas
AU - Danzer, Phil
AU - Miller, Amanda
AU - Montross, Kelsey
AU - Harrington, Deborah
AU - Westervelt, Holly
AU - Aylward, Elizabeth
AU - Rao, Stephen
AU - Moser, David J.
AU - Williams, Janet
AU - Downing, Nancy
AU - Magnotta, Vincent A.
AU - Vaidya, Jatin
AU - O’Leary, Daniel
AU - Kim, Eun Young
AU - Kim, Ji In
AU - Lourens, Spencer
AU - Zhang, Ying
AU - Lu, Wenjing
AU - Erwin, Cheryl
AU - Nance, Martha
AU - Evans, Jason
AU - Zschiegner, Roland
AU - Chiu, Edmond
AU - Loi, Samantha
AU - Chua, Phyllis
AU - Raymond, Lynn
AU - Ross, Christopher A.
AU - Mallonee, William M.
AU - Samii, Ali
AU - Jones, Randi
AU - Barker, Roger A.
AU - McCusker, Elizabeth
AU - Loy, Clement
AU - Orth, Michael
AU - Süßmuth, Sigurd
AU - Perlmutter, Joel
AU - Mazzoni, Pietro
N1 - Publisher Copyright:
© 2018 by the authors.
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
KW - Brain-derived neurotrophic factor
KW - Huntington’s disease
KW - Independent component analysis
KW - Supplementary motor
KW - Tropomyosin receptor kinase B
UR - http://www.scopus.com/inward/record.url?scp=85050259104&partnerID=8YFLogxK
U2 - 10.3390/brainsci8070116
DO - 10.3390/brainsci8070116
M3 - Article
C2 - 29932126
AN - SCOPUS:85050259104
SN - 2076-3425
VL - 8
JO - Brain Sciences
JF - Brain Sciences
IS - 7
M1 - 116
ER -