Relationship of a variant in the NTRK1 gene to white matter microstructure in young adults

Braskie, Meredith N., Jahanshad, Neda, Stein, Jason L., Barysheva, Marina, Johnson, Kori, McMahon, Katie L., de Zubicaray, Greig I., Martin, Nicholas G., Wright, Margaret J., Ringman, John M., Toga, Arthur W. and Thompson, Paul M. (2012) Relationship of a variant in the NTRK1 gene to white matter microstructure in young adults. The Journal of Neuroscience, 32 17: 5964-5972. doi:10.1523/JNEUROSCI.5561-11.2012

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Author Braskie, Meredith N.
Jahanshad, Neda
Stein, Jason L.
Barysheva, Marina
Johnson, Kori
McMahon, Katie L.
de Zubicaray, Greig I.
Martin, Nicholas G.
Wright, Margaret J.
Ringman, John M.
Toga, Arthur W.
Thompson, Paul M.
Total Author Count Override 12
Title Relationship of a variant in the NTRK1 gene to white matter microstructure in young adults
Journal name The Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
1529-2401
Publication date 2012-04-25
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.5561-11.2012
Open Access Status File (Publisher version)
Volume 32
Issue 17
Start page 5964
End page 5972
Total pages 9
Place of publication Washington, DC, United States
Publisher Society for Neuroscience
Collection year 2013
Language eng
Abstract The NTRK1 gene (also known as TRKA) encodes a high-affinity receptor for NGF, a neurotrophin involved in nervous system development and myelination. NTRK1 has been implicated in neurological function via links between the T allele at rs6336 (NTRK1-T) and schizophrenia risk. A variant in the neurotrophin gene, BDNF, was previously associated with white matter integrity in young adults, highlighting the importantce of neurotrophins to white matter development. We hypothesized that NTRK1-T would relate to lower fractional anisotropy in healthy adults. We scanned 391 healthy adult human twins and their siblings (mean age: 23.6 ± 2.2 years; 31 NTRK1-T carriers, 360 non-carriers) using 105-gradient diffusion tensor imaging at 4 tesla. We evaluated in brain white matter how NTRK1-T and NTRK1 rs4661063 allele A (rs4661063-A, which is in moderate linkage disequilibrium with rs6336) related to voxelwise fractional anisotropy-acommondiffusion tensor imaging measure of white matter microstructure. We used mixed-model regression to control for family relatedness, age, and sex. The sample was split in half to test reproducibility of results. The false discovery rate method corrected for voxelwise multiple comparisons. NTRK1-T and rs4661063-A correlated with lower white matter fractional anisotropy, independent of age and sex (multiple-comparisons corrected: false discovery rate critical p=0.038 forNTRK1-Tand0.013 for rs4661063-A). In each half-sample, theNTRK1-T effectwasreplicated in the cingulum, corpus callosum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, superior corona radiata, and uncinate fasciculus. Our results suggest that NTRK1-T is important for developing white matter microstructure.
Keyword Schizophrenia
Diffusion
Association
Risk
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Wed, 16 May 2012, 01:39:35 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging