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

PREDICT-HD Investigators and Coordinators of the Huntington

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article number116
JournalBrain Sciences
Volume8
Issue number7
DOIs
StatePublished - Jul 1 2018

Fingerprint

Huntington Disease
Cognition
trkB Receptor
Trail Making Test
Brain-Derived Neurotrophic Factor
Motor Cortex
Genes
Multivariate Analysis
Color
Alleles
Genotype
Gray Matter
Brain

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington’s disease. / PREDICT-HD Investigators and Coordinators of the Huntington.

In: Brain Sciences, Vol. 8, No. 7, 116, 01.07.2018.

Research output: Contribution to journalArticle

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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.",
keywords = "Brain-derived neurotrophic factor, Huntington’s disease, Independent component analysis, Supplementary motor, Tropomyosin receptor kinase B",
author = "{PREDICT-HD Investigators and Coordinators of the Huntington} and Ciarochi, {Jennifer A.} and Jingyu Liu and Vince Calhoun and Hans Johnson and Maria Misiura and Bockholt, {H. Jeremy} and Espinoza, {Flor A.} and Arvind Caprihan and Sergey Plis and Turner, {Jessica A.} and Paulsen, {Jane S.} and Long, {Jeffrey D.} and Johnson, {Hans J.} and Thomas Brashers-Krug and Phil Danzer and Amanda Miller and Kelsey Montross and Deborah Harrington and Holly Westervelt and Elizabeth Aylward and Stephen Rao and Moser, {David J.} and Janet Williams and Nancy Downing and Magnotta, {Vincent A.} and Jatin Vaidya and Daniel O’Leary and Kim, {Eun Young} and Kim, {Ji In} and Spencer Lourens and Ying Zhang and Wenjing Lu and Cheryl Erwin and Martha Nance and Jason Evans and Roland Zschiegner and Edmond Chiu and Samantha Loi and Phyllis Chua and Lynn Raymond and Ross, {Christopher A.} and Mallonee, {William M.} and Ali Samii and Randi Jones and Barker, {Roger A.} and Elizabeth McCusker and Clement Loy and Michael Orth and Sigurd S{\"u}{\ss}muth and Joanne Wojcieszek",
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AU - Danzer, Phil

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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

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AU - Kim, Eun Young

AU - Kim, Ji In

AU - Lourens, Spencer

AU - Zhang, Ying

AU - Lu, Wenjing

AU - Erwin, Cheryl

AU - Nance, Martha

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AU - Zschiegner, Roland

AU - Chiu, Edmond

AU - Loi, Samantha

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AU - Süßmuth, Sigurd

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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.

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KW - Brain-derived neurotrophic factor

KW - Huntington’s disease

KW - Independent component analysis

KW - Supplementary motor

KW - Tropomyosin receptor kinase B

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