Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22539856
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.
DATE PUBLISHED
2012 Apr 25
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/04/28 06:00
pubmed 2012/04/28 06:00
medline 2012/06/26 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Braskie MN Braskie Meredith N MN 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.
Jahanshad N Jahanshad Neda N
Stein JL Stein Jason L JL
Barysheva M Barysheva Marina M
Johnson K Johnson Kori K
McMahon KL McMahon Katie L KL
de Zubicaray GI de Zubicaray Greig I GI
Martin NG Martin Nicholas G NG
Wright MJ Wright Margaret J MJ
Ringman JM Ringman John M JM
Toga AW Toga Arthur W AW
Thompson PM Thompson Paul M PM
INVESTIGATORS
JOURNAL
VOLUME: 32
ISSUE: 17
TITLE: The Journal of neuroscience : the official journal of the Society for Neuroscience
ISOABBREVIATION: J. Neurosci.
YEAR: 2012
MONTH: Apr
DAY: 25
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1529-2401
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Neurosci
COUNTRY: United States
ISSNLINKING: 0270-6474
NLMUNIQUEID: 8102140
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
F31 MH087061 NIMH NIH HHS United States
F31MH087061 NIMH NIH HHS United States
P50 AG-16570 NIA NIH HHS United States
P50 AG016570 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 MH097268 NIMH NIH HHS United States
T15 LM007356 NLM NIH HHS United States
T15 LM07356 NLM NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Anisotropy
Brain anatomy & histology
Brain Mapping anatomy & histology
Diffusion Tensor Imaging anatomy & histology
Family Health anatomy & histology
Female anatomy & histology
Genotype anatomy & histology
Humans anatomy & histology
Image Processing, Computer-Assisted anatomy & histology
Linkage Disequilibrium anatomy & histology
Male anatomy & histology
Nerve Fibers, Myelinated physiology
Neural Pathways anatomy & histology
Polymorphism, Single Nucleotide genetics
Receptor, trkA genetics
Twins psychology
Young Adult psychology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 2.7.10.1 Receptor, trkA
OTHER ID's
OTHERID SOURCE
NIHMS373626 NLM
PMC3393752 NLM