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
23727532
TITLE
Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults.
ABSTRACT
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.
Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2013 Nov 15
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/12/03
revised 2013/05/20
accepted 2013/05/22
aheadofprint 2013/05/30
entrez 2013/06/04 06:00
pubmed 2013/06/04 06:00
medline 2014/04/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Braskie MN Braskie Meredith N MN Imaging Genetics Center, Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Kohannim O Kohannim Omid O
Jahanshad N Jahanshad Neda N
Chiang MC Chiang Ming-Chang MC
Barysheva M Barysheva Marina M
Toga AW Toga Arthur W AW
Ringman JM Ringman John M JM
Montgomery GW Montgomery Grant W GW
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
Thompson PM Thompson Paul M PM
INVESTIGATORS
JOURNAL
VOLUME: 82
ISSUE:
TITLE: NeuroImage
ISOABBREVIATION: Neuroimage
YEAR: 2013
MONTH: Nov
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1095-9572
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Neuroimage
COUNTRY: United States
ISSNLINKING: 1053-8119
NLMUNIQUEID: 9215515
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AG040060 NIA NIH HHS United States
EB007813 NIBIB NIH HHS United States
EB008281 NIBIB NIH HHS United States
EB008432 NIBIB NIH HHS United States
F30 AG041681 NIA NIH HHS United States
F30 AG041681 NIA NIH HHS United States
P41 EB015922 NIBIB NIH HHS United States
P50 AG016570 NIA NIH HHS United States
P50 AG16570 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB008281 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
T32 GM008042 NIGMS NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
BDNF
BPD
Bipolar disorder
DTI
DZ
Diffusion tensor imaging
FA
FDR
FLIRT
FSL's linear image registration tool
FWHM
Fractional anisotropy
HWE
Hardy–Weinberg equilibrium
IFO
ILF and SLF
LD
MAF
MZ
NT3
NTRK1
NTRK3 aka TRKC
OCD
Obsessive–compulsive disorder
SNP
Schizophrenia
Single nucleotide polymorphism
bipolar disorder
brain-derived neurotrophic factor
diffusion tensor imaging
dizygotic
false discovery rate
fractional anisotropy
full-width at half maximum
inferior and superior longitudinal fasciculi
inferior fronto-occipital fasciculus
linkage disequilibrium
minor allele frequencies
monozygotic
neurotrophic tyrosine kinase, receptor, type 1
neurotrophic tyrosine kinase, receptor, type 3 gene
neurotrophin 3'-nucleotidase
obsessive–compulsive disorder
single nucleotide polymorphism
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Anisotropy
Diffusion Tensor Imaging
Female
Genetic Predisposition to Disease genetics
Genotype genetics
Humans genetics
Image Processing, Computer-Assisted genetics
Linkage Disequilibrium genetics
Male genetics
Mental Disorders pathology
Nerve Fibers, Myelinated pathology
Polymorphism, Single Nucleotide pathology
Receptor, trkC genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 2.7.10.1 Receptor, trkC
OTHER ID's
OTHERID SOURCE
NIHMS487869 NLM
PMC3948328 NLM