Year: 2012
Type: article
Study design: Observational Study
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.
Source: Journal of Neuroscience
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Achievement Rewards for College Scientists Foundation, National Institutes of Health, Medical Research Council, Australian Research Council, National Health and Medical Research Council, National Institute on Aging, National Institute of Mental Health, National Institute of Biomedical Imaging and Bioengineering, National Institute of Child Health and Human Development, U.S. National Library of Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1121515656, G1372278137, G1550945203, G1734661113, G1951096767, G199256479, G2382774797, G2392088378, Genetic influences on the brain: A twin imaging study, G2594996237, G3109596333, G3157495676, G3199409182, G3495954047, G3544081313, G3553261625, G3632542342, G399895291, G411896701, Studying the Genetic Basis of Schizophrenia through Tract Alterations, G4741411087, G519183068, G5244094983, Computational Modeling of High-Field MR Images, G5520316217, G5618267289, G5850931412, G5938296382, G6460849299, G651483984, Genetics of moliness, G7928560463, The articulate brain, G9000092572, G9000166586, G9000179559, G9000264890
OpenAlex ID: W2139097975