Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults

Braskie, M. N., Kohannim, O., Jahanshad, N., Chiang, M. C., Barysheva, M., Toga, A. W., Ringman, J. M., Montgomery, G. W., McMahon, K. L., de Zubicaray, G. I., Martin, N. G., Wright, M. J., & Thompson, P. M. (2013) Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults. NeuroImage, 82, pp. 146-153.

View at publisher


The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. NTRK3 variants are putative risk factors for schizophrenia, bipolar disorder, and obsessive-compulsive disorder hoarding, suggesting that some NTRK3 variants may affect the brain.To test this, we scanned 392 healthy adult twins and their siblings (mean age, 23.6. ±. 2.2. years; range: 20-29. years) with 105-gradient 4-Tesla diffusion tensor imaging (DTI). We identified 18 single nucleotide polymorphisms (SNPs) in the NTRK3 gene that have been associated with neuropsychiatric disorders. We used a multi-SNP model, adjusting for family relatedness, age, and sex, to relate these variants to voxelwise fractional anisotropy (FA) - a DTI measure of white matter integrity.FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=. 0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.

Impact and interest:

6 citations in Scopus
Search Google Scholar™
8 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 85687
Item Type: Journal Article
Refereed: Yes
Keywords: Bipolar disorder, Diffusion tensor imaging, Fractional anisotropy, Obsessive-compulsive disorder, Schizophrenia, Single nucleotide polymorphism
DOI: 10.1016/j.neuroimage.2013.05.095
ISSN: 1095-9572
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 The Authors
Deposited On: 18 Sep 2015 06:35
Last Modified: 21 Sep 2015 05:18

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page