title: Relationship of a variant in the NTRK1 gene to white matter microstructure in young adults.
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 importance 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-a common diffusion 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 for NTRK1-T and 0.013 for rs4661063-A). In each half-sample, the NTRK1-T effect was replicated 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.
authors.affiliation: Laboratory of Neuro Imaging, Department of Neurology and Medical Imaging Informatics Group, Department of Radiology, University of California, Los Angeles-UCLA School of Medicine, Los Angeles, California 90095, USA.
authors.forename: Meredith N
authors.initials: MN
authors.lastname: Braskie
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.forename: Jason L
authors.initials: JL
authors.lastname: Stein
authors.forename: Marina
authors.initials: M
authors.lastname: Barysheva
authors.forename: Kori
authors.initials: K
authors.lastname: Johnson
authors.forename: Katie L
authors.initials: KL
authors.lastname: McMahon
authors.forename: Greig I
authors.initials: GI
authors.lastname: de Zubicaray
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000033:anatomy & histology*; D001931:Brain Mapping; D056324:Diffusion Tensor Imaging; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015810:Linkage Disequilibrium; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009434:Neural Pathways / Q000033:anatomy & histology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*; D014427:Twins / Q000235:genetics / Q000523:psychology; D055815:Young Adult
chemical_list: D020917:Receptor, trkA